Bladder cancer is the second most common urologic malignancy and accounts for approximately 90% of cancers of the urinary tract. Is the fourth most incident cancer in male and ninth in females [
1]. In industrialized countries, more than 90% of cases are originate in the urothelial epithelial cells (called urothelial cell carcinoma) [
2]. At diagnosis, 75% are non-invasive bladder cancer. The invasive bladder cancers may spread outside the bladder and affect other organs. Bladder cancer's staging, treatment and prognosis depend on how deeply it has invaded urinary bladder [
3].
Fortunately, about 80% of patients with non-muscle invasive disease can be successfully treated using the surgery. Historically, two-thirds of patients have tumour recurrence within 5 years. High-grade tumours have a significantly worse prognosis. Both high-grade T1 tumours and carcinoma
in situ have the potential to progress and even metastasize [
4]. Patients with invasive bladder cancer require a radical cystectomy. Controversy exists as to whether neoadjuvant or adjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite a number of randomised controlled trials. So far there are no data to confirm what is the best combination of treatments (neoadjuvant chemotherapy, adjuvant with or without radiotherapy) to treat invasive bladder cancer [
5]. The modest results with currently drugs, suggest the urgent need to identify new agents [
6]. Sirolimus is a macrocyclic lactone that was first discovered as a product of the soil bacteria
Streptomyces hygroscopicus. It was originally used as an immunosuppressant drug to help prevent rejection in organ transplantation, particularly in kidney transplant operations, but the authors of a number of recent reports have indicated that it may have other potential biological effects as an anti-cancer medicine [
7,
8]. Both the immunosuppressive and anti-cancer properties of sirolimus are due to the inhibition of the mammalian target of the sirolimus (mTOR) signalling pathway, which controls mRNA translation and induces angiogenesis and cell proliferation. Angiogenesis and a high proliferative index correspond to a poor prognosis for urothelial bladder cancer patients [
9,
10]. Sirolimus forms a complex with the immunophilin prolyl isomerase FK binding protein complex (FKBP-12) that binds with high affinity to mTOR [
11,
12]. This interaction inhibits mTOR kinase activity and subsequently decreases the phosphorylation of 4E binding protein-1 and the inhibition of the 40S ribosomal protein p70 S6 kinase [
13‐
15]. Sirolimus's antineoplasic effects have been related to its capacity to inhibit the translation machinery involved in the regulation of G1- to S-phase transition in cell cycle [
16,
17]. Cell growth and proliferation in numerous cancer types are often regulated by the mammalian target of sirolimus (mTOR) pathway through p7056 kinase, ribosomal S6 protein, and eukaryotic initiation factor 4 E-binding protein 1 [
18]. Recently there has been an enormous increase in our understanding of the molecular mechanisms underlying sirolimus's therapeutic anti-cancer properties. Alterations in the pathway regulating mTOR occur in many solid malignancies including bladder cancer.
In vitro and
in vivo models of bladder cancer have established the importance of the mTOR pathway in controlling cancer progression and metastasis [
19]. The T24 cell line has been established from a highly malignant grade III human urinary bladder carcinoma [
20]. This cell line can be easily grown
in vitro and has been extensively used to evaluate the therapeutic effects of several anticancer drugs. Here, we describe the preliminary results of the study of the therapeutic effect of sirolimus against human T24 bladder cancer cell line
in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for assessing cell proliferation and Trypan blue for assessing cell viability.