Synthetic Smac peptide enhances chemo-sensitivity of bladder cancer cells.
The effects of synthetic Smac peptide (SmacN7) on chemotherapeutic sensitivity of bladder cancer cells were investigated. SmacN7 penetratin peptide was synthesized and delivered into T24 cells. MTT assay was used to evaluate the viability of T24 cells induced by low-dosage of MMC. Flow cytometry was used to analyze the proportions of apoptosis. Western blot was used to detect the expression of XIAP and Caspase-3. The activity of Caspase-3 was measured and the effect of SmacN7 combined with MMC on T24 cell lines was also determined. The results showed that SmacN7 penetratin peptide could successfully interact with endogenous XIAP, increase the proportions of apoptosis of T24 cell lines induced by low-dosage of MMC in a dose-and time-dependent manner. An obvious down-regulation of XIAP expression and up-regulation of Caspase-3 was identified by Western blot. The activity of Caspase-3 in experimental group was significantly increased as compared with that in the control group. As compared with MMC group, the viability of T24 cells in SmacN7 penetratin peptide+MMC group was markedly decreased to 2.22 and 3.61 folds at 24 h and 48 h respectively. It was concluded that SmacN7 penetratin peptide could act as a cell-permeable IAP inhibitor, inhibit the proliferation, induce apoptosis and enhance the chemo-sensitivity of bladder cancer cells to MMC. These findings indicate that SmacN7 penetratin peptide may be a very promising ageut for bladder cancer treatment when used in combination with chemotherapy.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. wangjing424@126.com
Jing
J
Wang
Fuqing
F
Zeng
Liang
L
Wang
Zhaohui
Z
Zhu
Guosong
G
Jiang
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000502:physiology*; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D053148:Caspase 3; C022616:thiazolyl blue