The mechanism and inhibitory effect of recombinant human P53 adenovirus injection combined with paclitaxel on human cervical cancer cell HeLa

Y.-G. Liu, X.-L. Zheng, F.-M. Liu

Department of Obstetrics and Gynecology, Xuzhou Medical College, Affiliated to Xuzhou Municipal Hospital, Xuzhou, Jiangsu, China. zxl9711143@163.com

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• Oncology

OBJECTIVE: To investigate the effect of recombinant human p53 adenovirus injection combined with paclitaxel on human cervical cancer HeLa cell proliferation, apoptosis and expression of vascular endothelial growth factor (VEGF).

MATERIALS AND METHODS: Detection of effects of paclitaxel, rAd-p53, and drug combination on the proliferation of HeLa cells by MTT method. Detection of effects of paclitaxel, rAd-p53, and drug combination on the proliferation of HeLa cells by diamidino-phenyl-indole (DAPI) staining. Detection of effects of paclitaxel, rAd-p53, and drug combination on the expression of VEGF of HeLa cells by Western blotting.

RESULTS: Paclitaxel, rAd-p53 alone or in combination could inhibit the proliferation of HeLa cells in 24-72 h. The inhibition is time dependent and dose dependent. Inhibition of HeLa cells in the combination group was significantly higher than single use of paclitaxel group and rAd-P53 group (p < 0.05). The combined effect of the coefficient of drug interaction (CDI) value was CDI < 1, showing that the two have a synergistic effect. Cell inhibition rate combined group of RAd-P53 (5 × l07 vp/mL) and paclitaxel (3 µg/mL) 48 h after application is higher than that of monotherapy group [(54.0 ± 0.92) % vs. (31.8 ± 0.58) %, (27.2 ± 0.55) %, p < 0.05]. The apoptosis rate of HeLa cells in combination group was significantly higher than that in paclitaxel group, rAd-p53 alone group [(83 ± 0.07) % vs. (11 ± 0.01) %, (36 ± 0.04) %, (62 ± 0.05) %, p < 0.05]. Expression of VEGF in HeLa cells of combination group was significantly lower than that of the two single drug groups. Expression of VEGF in HeLa cells was decreased by (81 + 0.08) %, (45 + 0.07) % and (60 + 0.06) % (p < 0.05), respectively.

CONCLUSIONS: The effect of rAd-p53 and paclitaxel inhibiting HeLa cell proliferation and induction of apoptosis is better than the single drug. Its mechanism may be related to the down-regulation of VEGF.

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