Zhonghua yi xue za zhi · 2015
[Mechanism of thioridazine plus medroxyprogesterone in the treatment of endometrial cancer].
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Meng Qiong, Sun Xiao, Wang Jing, Wang Yudong
Аннотация
OBJECTIVE: To explore the in vitro effects of thioridazine (THIO) plus medroxyprogesterone (MPA) on the proliferation and apoptosis of endometrial cancer cell lines (Ishikawa & KLE) and examine the mechanism in the treatment of endometrial cancer.
METHODS: CCK-8 assay was employed for detecting the influence of THIO plus MPA on the proliferation and apoptosis of endometrial cancer cells (ISK & KLE). And the concentration and timepoints of drugs were determined according to the results. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the expression levels of PRB, DRD2 and p-AKT/AKT in PI3K/AKT signal pathway. Flow cytometry was applied for detecting the apoptosis of combination (THIO+MPA) and MPA groups.
RESULTS: Compared to MPA group, the proliferation inhibiting effect of combination group increased significantly in ISK and KLE cells (52.5% ± 2.6% vs 37.3% ± 0.3%, P < 0.05; 97.7% ± 0.7% vs 50.0% ± 0.4%, P < 0.001); the apoptotic rates increased (34.0% ± 1.4% vs 50.5% ± 2.4%, P < 0.01; 5.5% ± 3.6% vs 11.3% ± 0.7%, P < 0.01); the expression levels of PRB and DRD2 were up-regulated (all P < 0.05). And the ratio of p-AKT/AKT decreased obviously.
CONCLUSION: Thioridazine significantly enhances the effects of MPA on proliferative inhibition and apoptotic promotion in endometrial cancer cells. And it may be associated with the PRB/DRD2-mediated PI3K/AKT signal pathway.
METHODS: CCK-8 assay was employed for detecting the influence of THIO plus MPA on the proliferation and apoptosis of endometrial cancer cells (ISK & KLE). And the concentration and timepoints of drugs were determined according to the results. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the expression levels of PRB, DRD2 and p-AKT/AKT in PI3K/AKT signal pathway. Flow cytometry was applied for detecting the apoptosis of combination (THIO+MPA) and MPA groups.
RESULTS: Compared to MPA group, the proliferation inhibiting effect of combination group increased significantly in ISK and KLE cells (52.5% ± 2.6% vs 37.3% ± 0.3%, P < 0.05; 97.7% ± 0.7% vs 50.0% ± 0.4%, P < 0.001); the apoptotic rates increased (34.0% ± 1.4% vs 50.5% ± 2.4%, P < 0.01; 5.5% ± 3.6% vs 11.3% ± 0.7%, P < 0.01); the expression levels of PRB and DRD2 were up-regulated (all P < 0.05). And the ratio of p-AKT/AKT decreased obviously.
CONCLUSION: Thioridazine significantly enhances the effects of MPA on proliferative inhibition and apoptotic promotion in endometrial cancer cells. And it may be associated with the PRB/DRD2-mediated PI3K/AKT signal pathway.