OBJECTIVE: To study the effects of podophyllotoxin derivative QW-83 on human cervical cancer HeLa cell apoptosis and its mechanism. METHODS: After treated with 0(negative control), 0.01, 0.1, 1 and 10 μmol/L QW-83 and positive drug etoposide (VP-16) for 48 h, proliferation inhibition rate and IC50 of HeLa cell were determined by MTT assay. The morphological changes of HeLa cell were observed by Hochest 33342 staining after treated with QW-83 [0 (negative control), 2.5, 5, 10 μmol/L] for 48 h; flow cytometry was used to detect apoptosis rate; semi quantitative RT-PCR was adopted to detect the expression of apoptosis related gene P53, Bax, Casepase-3, Casepase-8, Casepase-9 and Bcl-2 mRNA. RESULTS: Compared with negative control, 1, 10 μmol/L VP-16 and QW-83 had obvious proliferation inhibition effect on HeLa cells (P<0.05 or P<0.01), and IC50 were (5.11±0.43) μmol/L and (4.96±0.54) μmol/L. Hochest 33342 staining results showed QW-83 could obviously induce cells apoptosis and nuclear pyknosis. Flow cytometry showed QW-83 could increase apoptosis rate in concentration-dependent manner, being 16.89%-62.56%. RT-PCR showed mRNA expression of P53, Bax, Caspase-3, Casepase-8 and Casepase-9, Bcl-2/Bax increased, while mRNA expression of Bcl-2 decreased after treated with QW-83 (P<0.05). CONCLUSIONS: Podophyllotoxin derivative QW- 83 can induce HeLa cell apoptosis, and its mechanism may be associated with regulate mRNA expression of apoptosis related gene.
关键词
鬼臼毒素衍生物QW-83人宫颈癌HeLa细胞抗肿瘤活性凋亡相关基因依托泊苷
Keywords
Podophyllotoxin derivativeQW-83Human cervical cancer HeLa cellAntitumor activityApoptosis-related geneEtoposide