[Proliferation effects of sirolimus, cyclosporine A and mycophenolate mofetil on human transitional cell carcinoma cells].

ABSTRACT

OBJECTIVE: To compared the effects of three immunosuppressive agents, i.e. sirolimus (SRL), cyclosporine A (CsA) and mycophenolate mofetil (MMF), with different mechanisms of action on the in vitro growth of various tumor cell lines of human transitional cell carcinoma of bladder cell lines EJ and T24 and in vivo growth of cell line of EJ in nude mice model. METHODS: The effects of SRL, CsA and MMF on the proliferation of transitional cell carcinoma of bladder cell lines were examined with the method of methyl thiazolyl tetrazolium (MTT). The effects of these immunosuppressants on tumor growth and metastasis were explored in a nude mice model with human transitional cell carcinoma of bladder cell line EJ. Forty-two nude mice were divided into 7 groups to receive normal saline (control), SRL, CsA, MMF, SRL + CsA, SRL + MMF and CsA + MMF respectively (n = 6 each). RESULTS: The in vitro cell proliferation was inhibited by SRL and MMF versus the control groups. But no obvious inhibition of proliferation was observed at < 1000 ng/ml in the CsA-treated group. In the in vivo nude mice mode, the tumor volume of SRL, CsA group were lower than that in control group ((441 ± 231), (463 ± 110) vs (1032 ± 382) mm(3), both P < 0.05). In the in vivo nude mice mode of EJ treated by SRL, CsA, SRL + CsA, SRL + MMF and CsA + MMF, tumor volume at Day 23 was the lowest in the SRL + CsA group ((191 ± 92) vs (1032 ± 382) mm(3), P < 0.05). There was an inhibition of 75.26% in SRL + CsA group versus the control groups. CONCLUSIONS: SRL and MMF demonstrate dose-dependent antiproliferative effects in human transitional cell carcinoma of bladder cell both in vitro and in vivo. CsA can inhibit the growth of human transitional cell carcinoma of bladder cell lines EJ cells in vivo.