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02.12.2015 | Original Article

Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma

verfasst von: Ipsita Pal, Kaushik Kumar Dey, Madhuri Chaurasia, Sheetal Parida, Subhayan Das, Y. Rajesh, Kulbhushan Sharma, Tamohan Chowdhury, Mahitosh Mandal

Erschienen in: Tumor Biology | Ausgabe 5/2016

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Abstract

Amplification of PI3K-Akt pathway promotes radioresistance in various cancers including colorectal carcinoma. Local recurrence in colon cancer causes poor prognosis affecting overall survival of cancer-affected patient population. To avoid local recurrence, pre-operative or post-operative additional radiotherapy is given. However, main concern regarding radiotherapy is to increase the radiosensitivity of malignant cell without hampering the activities of normal cells. In this context, addition of two or more than two chemotherapeutic drugs as a radiosensitizer is a common practice in radiation biology. BI-69A11 earlier showed potential apoptosis-inducing effect in melanoma and colon carcinoma. Celecoxib showed anti-cancer effects in both COX-2 dependent and independent pathways and used to act as a radiosensitizing enhancer. Here, we suggest that the combination of BI-69A11 and celecoxib inhibits the phosphorylation of ataxia telangiectasia mutated (ATM) kinase and DNA-PK responsible for ionizing radiation (IR)-induced double-strand break (DSB) repair. Moreover, the combinatorial effect of BI-69A11 and celecoxib attenuates the IR-induced G2/M cell cycle arrest. Furthermore, this combination also impairs IR-induced activation of Akt and downstream targets of ATM. This might lead to induced activation of apoptotic pathway after triple therapy treatment modulating pro-apoptotic and anti-apoptotic proteins. This activation of apoptotic pathway also showed the interdependence of PUMA and BAD in triple combination-treated colon cancer cells in a p53 independent manner. This study reveals the therapeutic potential of the triple combination therapy in prevention of radioresistance. Besides, it also demonstrates the cytotoxic effects of triple combination therapy in colon cancer. This study shows utility and potential implication on safety of the patients undergoing radiation therapy.

Hahnloser D, Haddock MG, Nelson H. Intraoperative radiotherapy in the multimodality approach to colorectal cancer. Surg Oncol Clin N Am. 2003;12:993–1013. ix.CrossRefPubMed

Hocht S, Hammad R, Thiel HJ, Wiegel T, Siegmann A, Willner J, et al. Recurrent rectal cancer within the pelvis. A multicenter analysis of 123 patients and recommendations for adjuvant radiotherapy. Strahlenther Onkol. 2004;180:15–20.CrossRefPubMed

Horgan AF, Finlay IG. Preoperative staging of rectal cancer allows selection of patients for preoperative radiotherapy. Br J Surg. 2000;87:575–9.CrossRefPubMed

Schlemmer HP, Becker M, Bachert P, Dietz A, Rudat V, Vanselow B, et al. Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck carcinoma during simultaneous radiochemotherapy. Cancer Res. 1999;59:2363–9.PubMed

Lawrence TS, Davis MA, Maybaum J. Dependence of 5-fluorouracil-mediated radiosensitization on DNA-directed effects. Int J Radiat Oncol Biol Phys. 1994;29:519–23.CrossRefPubMed

Chen AY, Chou R, Shih SJ, Lau D, Gandara D. Enhancement of radiotherapy with DNA topoisomerase I-targeted drugs. Crit Rev Oncol Hematol. 2004;50:111–9.CrossRefPubMed

Chen AY, Okunieff P, Pommier Y, Mitchell JB. Mammalian DNA topoisomerase I mediates the enhancement of radiation cytotoxicity by camptothecin derivatives. Cancer Res. 1997;57:1529–36.PubMed

Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7:573–84.CrossRefPubMed

Espinosa M, Martinez M, Aguilar JL, Mota A, De la Garza JG, Maldonado V, et al. Oxaliplatin activity in head and neck cancer cell lines. Cancer Chemother Pharmacol. 2005;55:301–5.CrossRefPubMed

10.

Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res. 2000;6:2166–74.PubMed

11.

Dittmann K, Mayer C, Rodemann HP. Inhibition of radiation-induced EGFR nuclear import by C225 (cetuximab) suppresses DNA-PK activity. Radiother Oncol. 2005;76:157–61.CrossRefPubMed

12.

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMed

13.

Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.CrossRefPubMed

14.

Janjan NA, Abbruzzese J, Pazdur R, Khoo VS, Cleary K, Dubrow R, et al. Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol. 1999;51:153–60.CrossRefPubMed

15.

Janjan NA, Crane C, Feig BW, Cleary K, Dubrow R, Curley S, et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol. 2001;24:107–12.CrossRefPubMed

16.

Krishnan S, Janjan NA, Skibber JM, Rodriguez-Bigas MA, Wolff RA, Das P, et al. Phase ii study of capecitabine (xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66:762–71.CrossRefPubMed

17.

Rodel C, Liersch T, Hermann RM, Arnold D, Reese T, Hipp M, et al. Multicenter phase ii trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol. 2007;25:110–7.CrossRefPubMed

18.

Mohiuddin M, Winter K, Mitchell E, Hanna N, Yuen A, Nichols C, et al. Randomized phase ii study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol. 2006;24:650–5.CrossRefPubMed

19.

Chistiakov DA, Voronova NV, Chistiakov PA. Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients. Acta Oncol. 2008;47:809–24.CrossRefPubMed

20.

Jang NY, Kim DH, Cho BJ, Choi EJ, Lee JS, Wu HG, et al. Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer. BMC Cancer. 2015;15:89.CrossRefPubMedPubMedCentral

21.

Franke TF. PI3K/Akt: getting it right matters. Oncogene. 2008;27:6473–88.CrossRefPubMed

22.

Manning BD, Cantley LC. Akt/Pkb signaling: navigating downstream. Cell. 2007;129:1261–74.CrossRefPubMedPubMedCentral

23.

Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK, et al. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 1995;81:727–36.CrossRefPubMed

24.

Contessa JN, Abell A, Valerie K, Lin PS, Schmidt-Ullrich RK. ERBB receptor tyrosine kinase network inhibition radiosensitizes carcinoma cells. Int J Radiat Oncol Biol Phys. 2006;65:851–8.CrossRefPubMed

25.

Li B, Yuan M, Kim IA, Chang CM, Bernhard EJ, Shu HK. Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/Akt pathway and promotes radioresistance in cells of astrocytic origin. Oncogene. 2004;23:4594–602.CrossRefPubMed

26.

Toulany M, Dittmann K, Kruger M, Baumann M, Rodemann HP. Radioresistance of K-RAS mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-Akt pathway. Radiother Oncol. 2005;76:143–50.CrossRefPubMed

27.

Toulany M, Dittmann K, Baumann M, Rodemann HP. Radiosensitization of Ras-mutated human tumor cells in vitro by the specific EGF receptor antagonist BIBX1382BS. Radiother Oncol. 2005;74:117–29.CrossRefPubMed

28.

Zhang T, Cui GB, Zhang J, Zhang F, Zhou YA, Jiang T, et al. Inhibition of PI3 kinases enhances the sensitivity of non-small cell lung cancer cells to ionizing radiation. Oncol Rep. 2010;24:1683–9.PubMed

29.

Li HF, Kim JS, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol. 2009;4:43.CrossRefPubMedPubMedCentral

30.

Bussink J, van der Kogel AJ, Kaanders JH. Activation of the PI3-K/Akt pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol. 2008;9:288–96.CrossRefPubMed

31.

Zhan M, Han ZC. Phosphatidylinositide 3-kinase/Akt in radiation responses. Histol Histopathol. 2004;19:915–23.PubMed

32.

Kim IA, Bae SS, Fernandes A, Wu J, Muschel RJ, McKenna WG, et al. Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Cancer Res. 2005;65:7902–10.PubMed

33.

Liu Y, Cui B, Qiao Y, Zhang Y, Tian Y, Jiang J, et al. Phosphoinositide-3-kinase inhibition enhances radiosensitization of cervical cancer in vivo. Int J Gynecol Cancer. 2011;21:100–5.CrossRefPubMed

34.

Brognard J, Clark AS, Ni Y, Dennis PA. Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. 2001;61:3986–97.PubMed

35.

Prevo R, Deutsch E, Sampson O, Diplexcito J, Cengel K, Harper J, et al. Class i PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity. Cancer Res. 2008;68:5915–23.CrossRefPubMed

36.

Mukherjee B, Tomimatsu N, Amancherla K, Camacho CV, Pichamoorthy N, Burma S. The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKcs-mediated DNA damage responses. Neoplasia. 2012;14:34–43.CrossRefPubMedPubMedCentral

37.

Kao GD, Jiang Z, Fernandes AM, Gupta AK, Maity A. Inhibition of phosphatidylinositol-3-oh kinase/Akt signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J Biol Chem. 2007;282:21206–12.CrossRefPubMedPubMedCentral

38.

Toulany M, Minjgee M, Kehlbach R, Chen J, Baumann M, Rodemann HP. ERBB2 expression through heterodimerization with ERBB1 is necessary for ionizing radiation- but not EGF-induced activation of Akt survival pathway. Radiother Oncol. 2010;97:338–45.CrossRefPubMed

39.

Fraser M, Harding SM, Zhao H, Coackley C, Durocher D, Bristow RG. MRE11 promotes Akt phosphorylation in direct response to DNA double-strand breaks. Cell Cycle. 2011;10:2218–32.CrossRefPubMed

40.

Toulany M, Lee KJ, Fattah KR, Lin YF, Fehrenbacher B, Schaller M, et al. Akt promotes post-irradiation survival of human tumor cells through initiation, progression, and termination of DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Res. 2012;10:945–57.CrossRefPubMed

41.

Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001;27:247–54.CrossRefPubMed

42.

Iliakis G, Wang H, Perrault AR, Boecker W, Rosidi B, Windhofer F, et al. Mechanisms of DNA double strand break repair and chromosome aberration formation. Cytogenet Genome Res. 2004;104:14–20.CrossRefPubMed

43.

Hsu FM, Zhang S, Chen BP. Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment. Transl Cancer Res. 2012;1:22–34.PubMedPubMedCentral

44.

Wolff E, Delisle B, Corrieu G, Gibert H. Freeze-drying of streptococcus thermophilus: a comparison between the vacuum and the atmospheric method. Cryobiology. 1990;27:569–75.CrossRefPubMed

45.

Chen BP, Uematsu N, Kobayashi J, Lerenthal Y, Krempler A, Yajima H, et al. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem. 2007;282:6582–7.CrossRefPubMed

46.

Bozulic L, Surucu B, Hynx D, Hemmings BA. PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival. Mol Cell. 2008;30:203–13.CrossRefPubMed

47.

Meyn RE. Linking PTEN with genomic instability and DNA repair. Cell Cycle. 2009;8:2322–3.CrossRefPubMed

48.

Affolter A, Drigotas M, Fruth K, Schmidtmann I, Brochhausen C, Mann WJ, et al. Increased radioresistance via G12S K-RAS by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer. Head Neck. 2013;35:220–8.CrossRefPubMed

49.

Choi MJ, Park EJ, Oh JH, Min KJ, Yang ES, Kim YH, et al. Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation. Chem Biol Interact. 2011;190:102–8.CrossRefPubMed

50.

Toulany M, Kasten-Pisula U, Brammer I, Wang S, Chen J, Dittmann K, et al. Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-Akt signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res. 2006;12:4119–26.CrossRefPubMed

51.

Viniegra JG, Martinez N, Modirassari P, Hernandez Losa J, Parada Cobo C, Sanchez-Arevalo Lobo VJ, et al. Full activation of Pkb/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem. 2005;280:4029–36.CrossRefPubMed

52.

Khalil A, Morgan RN, Adams BR, Golding SE, Dever SM, Rosenberg E, et al. ATM-dependent ERK signaling via Akt in response to DNA double-strand breaks. Cell Cycle. 2011;10:481–91.CrossRefPubMedPubMedCentral

53.

Hawkins AJ, Golding SE, Khalil A, Valerie K. DNA double-strand break—induced pro-survival signaling. Radiother Oncol. 2011;101:13–7.CrossRefPubMedPubMedCentral

54.

Park JS, Jun HJ, Cho MJ, Cho KH, Lee JS, Zo JI, et al. Radiosensitivity enhancement by combined treatment of celecoxib and gefitinib on human lung cancer cells. Clin Cancer Res. 2006;12:4989–99.CrossRefPubMed

55.

Maier TJ, Schilling K, Schmidt R, Geisslinger G, Grosch S. Cyclooxygenase-2 (COX-2)-dependent and -independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. Biochem Pharmacol. 2004;67:1469–78.CrossRefPubMed

56.

Hsiao PW, Chang CC, Liu HF, Tsai CM, Chiu TH, Chao JI. Activation of p38 mitogen-activated protein kinase by celecoxib oppositely regulates survivin and gamma-H2AX in human colorectal cancer cells. Toxicol Appl Pharmacol. 2007;222:97–104.CrossRefPubMed

57.

Sakoguchi-Okada N, Takahashi-Yanaga F, Fukada K, Shiraishi F, Taba Y, Miwa Y, et al. Celecoxib inhibits the expression of survivin via the suppression of promoter activity in human colon cancer cells. Biochem Pharmacol. 2007;73:1318–29.CrossRefPubMed

58.

Bijman MN, Hermelink CA, van Berkel MP, Laan AC, Janmaat ML, Peters GJ, et al. Interaction between celecoxib and docetaxel or cisplatin in human cell lines of ovarian cancer and colon cancer is independent of COX-2 expression levels. Biochem Pharmacol. 2008;75:427–37.CrossRefPubMed

59.

Liu DB, Long GX, Mei Q, Wang JF, Hu GY, Gan L, et al. Anticancer effects of celecoxib through inhibiton of STAT3 phosphorylation and Akt phosphorylation in nasopharyngeal carcinoma cell lines. Pharmazie. 2014;69:358–61.PubMed

60.

Kim YM, Pyo H. Cooperative enhancement of radiosensitivity after combined treatment of 17-(allylamino)-17-demethoxygeldanamycin and celecoxib in human lung and colon cancer cell lines. DNA Cell Biol. 2012;31:15–29.CrossRefPubMedPubMedCentral

61.

Xia S, Zhao Y, Yu S, Zhang M. Activated PI3K/Akt/COX-2 pathway induces resistance to radiation in human cervical cancer HeLa cells. Cancer Biother Radiopharm. 2010;25:317–23.CrossRefPubMed

62.

Kim YM, Jeong IH, Pyo H. Celecoxib enhances the radiosensitizing effect of 7-hydroxystaurosporine (UCN-01) in human lung cancer cell lines. Int J Radiat Oncol Biol Phys. 2012;83:e399–407.CrossRefPubMed

63.

Gaitonde S, De SK, Tcherpakov M, Dewing A, Yuan H, Riel-Mehan M, et al. Bi-69a11-mediated inhibition of Akt leads to effective regression of xenograft melanoma. Pigment Cell Melanoma Res. 2009;22:187–95.CrossRefPubMedPubMedCentral

64.

Feng Y, Barile E, De SK, Stebbins JL, Cortez A, Aza-Blanc P, et al. Effective inhibition of melanoma by Bi-69a11 is mediated by dual targeting of the Akt and NF-kappaB pathways. Pigment Cell Melanoma Res. 2011;24:703–13.CrossRefPubMedPubMedCentral

65.

Barile E, De SK, Feng Y, Chen V, Yang L, Ronai Z, et al. Synthesis and SAR studies of dual Akt/NF-kappaB inhibitors against melanoma. Chem Biol Drug Des. 2013;82:520–33.CrossRefPubMedPubMedCentral

66.

Forino M, Jung D, Easton JB, Houghton PJ, Pellecchia M. Virtual docking approaches to protein kinase B inhibition. J Med Chem. 2005;48:2278–81.CrossRefPubMed

67.

Sarkar S, Mazumdar A, Dash R, Sarkar D, Fisher PB, Mandal M. Zd6474, a dual tyrosine kinase inhibitor of EGFR and VEGFR-2, inhibits MAPK/ERK and Akt/PI3-K and induces apoptosis in breast cancer cells. Cancer Biol Ther. 2010;9:592–603.CrossRefPubMed

68.

Buch K, Peters T, Nawroth T, Sanger M, Schmidberger H, Langguth P. Determination of cell survival after irradiation via clonogenic assay versus multiple MTT assay—a comparative study. Radiat Oncol. 2012;7:1.CrossRefPubMedPubMedCentral

69.

Mandal M, Adam L, Mendelsohn J, Kumar R. Nuclear targeting of BAX during apoptosis in human colorectal cancer cells. Oncogene. 1998;17:999–1007.CrossRefPubMed

70.

Rajput S, Kumar BN, Dey KK, Pal I, Parekh A, Mandal M. Molecular targeting of Akt by thymoquinone promotes G(1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci. 2013;93:783–90.CrossRefPubMed

71.

Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, et al. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013;8:e61342.CrossRefPubMedPubMedCentral

72.

Saha B, Adhikary A, Ray P, Saha S, Chakraborty S, Mohanty S, et al. Restoration of tumor suppressor p53 by differentially regulating pro- and anti-p53 networks in HPV-18-infected cervical cancer cells. Oncogene. 2012;31:173–86.CrossRefPubMed

73.

Firsanov DV, Solovjeva LV, Svetlova MP. H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues. Clin Epigenetics. 2011;2:283–97.CrossRefPubMedPubMedCentral

74.

Kumar A, Fernandez-Capetillo O, Carrera AC. Nuclear phosphoinositide 3-kinase beta controls double-strand break DNA repair. Proc Natl Acad Sci U S A. 2010;107:7491–6.CrossRefPubMedPubMedCentral

75.

Norbury CJ, Zhivotovsky B. DNA damage-induced apoptosis. Oncogene. 2004;23:2797–808.CrossRefPubMed

76.

Gardai SJ, Hildeman DA, Frankel SK, Whitlock BB, Frasch SC, Borregaard N, et al. Phosphorylation of BAX Ser184 by Akt regulates its activity and apoptosis in neutrophils. J Biol Chem. 2004;279:21085–95.CrossRefPubMed

77.

Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and Mcl-1 protein-protein interactions with BAX, BAK, BAD, or BIM and induces apoptosis in a BAX- and BIM-dependent manner. J Biol Chem. 2011;286:9382–92.CrossRefPubMed

78.

Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91:231–41.CrossRefPubMed

79.

Yu J, Zhang L. PUMA, a potent killer with or without p53. Oncogene. 2008;27 Suppl 1:S71–83.CrossRefPubMedPubMedCentral

80.

Toruno C, Carbonneau S, Stewart RA, Jette C. Interdependence of BAD and PUMA during ionizing-radiation-induced apoptosis. PLoS One. 2014;9:e88151.CrossRefPubMedPubMedCentral

81.

Ravoori S, Feng Y, Neale JR, Jeyabalan J, Srinivasan C, Hein DW, et al. Dose-dependent reduction of 3,2′-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib. Mutat Res. 2008;638:103–9.CrossRefPubMed

82.

Xiao H, Zhang Q, Lin Y, Reddy BS, Yang CS. Combination of atorvastatin and celecoxib synergistically induces cell cycle arrest and apoptosis in colon cancer cells. Int J Cancer. 2008;122:2115–24.CrossRefPubMed

83.

Grosch S, Tegeder I, Niederberger E, Brautigam L, Geisslinger G. COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib. FASEB J. 2001;15:2742–4.PubMed

84.

Yang Z, Xiao H, Jin H, Koo PT, Tsang DJ, Yang CS. Synergistic actions of atorvastatin with gamma-tocotrienol and celecoxib against human colon cancer HT29 and HCT116 cells. Int J Cancer. 2010;126:852–63.PubMedPubMedCentral

85.

Liu JP, Wei HB, Zheng ZH, Guo WP, Fang JF. Celecoxib increases retinoid sensitivity in human colon cancer cell lines. Cell Mol Biol Lett. 2010;15:440–50.CrossRefPubMed

86.

Uddin S, Ahmed M, Hussain A, Assad L, Al-Dayel F, Bavi P, et al. Cyclooxygenase-2 inhibition inhibits PI3K/Akt kinase activity in epithelial ovarian cancer. Int J Cancer. 2010;126:382–94.CrossRefPubMed

87.

Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage. Oncogene. 1999;18:7644–55.CrossRefPubMed

88.

He K, Zheng X, Zhang L, Yu J. HSP90 inhibitors promote p53-dependent apoptosis through PUMA and BAX. Mol Cancer Ther. 2013;12:2559–68.CrossRefPubMed

Titel: Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma
verfasst von: Ipsita Pal
Kaushik Kumar Dey
Madhuri Chaurasia
Sheetal Parida
Subhayan Das
Y. Rajesh
Kulbhushan Sharma
Tamohan Chowdhury
Mahitosh Mandal
Publikationsdatum: 02.12.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 5/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4399-6

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Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma

Abstract

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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