PURPOSE: To evaluate the sensitivity of apoptosis-stimulating protein of p53 (ASPP) and P-glycoprotein (P-gp) to the recombinant human adenovirus-p53 (rAd-p53) combined with neoadjuvant chemotherapy for locally advanced cervical cancer and their predictive value for efficacy. METHODS:80 patients with histopathologically diagnosed locally advanced cervical cancer (stage Ib2-IIa2) and operative treatment from February 2009 to June 2013 were enrolled and randomly divided into 3 groups: radical hysterectomy group (RH group, n=30), simple intravenous chemotherapy with cisplatin paclitaxel group (TP group, n=30) and gene therapy + intravenous chemotherapy group with cisplatin+paclitaxel (rAd-p53 + TP group, n=20). Patients in the RH group were directly operated, those in the TP group were treated with TP chemotherapy for 2 courses, and those in the rAd-p53 + TP group were treated with the same chemotherapy regimen and the rAd-p53 agent (1×1012 virus particles) was injected for the first time 3 days after chemotherapy for 3 times. The changes in tumor volume, adverse reactions and survival of patients in the TP group and rAd-p53 + TP group, and the levels of p53, ASPP2, inhibitory member of the ASPP family (iASPP) and P-gp in postoperative tumor tissues in the 3 groups were evaluated. RESULTS: The efficacy was evaluated for all patients in the TP group and rAd-p53 + TP group 3 weeks after chemotherapy. The tumor was reduced by 10.90±2.62 cm2 after medication in the TP group and 15.25±4.01 cm2 after medication in rAd-p53 + TP group, and the difference was statistically significant. The response rate [complete response (CR) + partial response (PR)] was 76.7% in the TP group and 95% in the rAd-p53 + TP group, with statistically significant difference. The positive expression rate of p53 protein showed a gradual decreasing trend in the RH group, TP group and rAd-p53 + TP group, with statistically significant difference (p<0.05). The positive expression rate of ASPP2 displayed a gradual increasing trend in the RH group, TP group and rAd-p53 + TP group, without statistically significant difference (p>0.05). The positive expression rate of iASPP was different and gradually declined in the RH group, TP group and rAd-p53 + TP group (p<0.05). Moreover, the positive expression rate of P-gp was also different among the 3 groups, and it was increased in the TP group, while it was decreased in the RH and rAd-p53 + TP group (p<0.05). CONCLUSION: The intratumor injection of rAd-p53 into patients with cervical cancer is safe and effective, showing a new way in the gene therapy of cervical cancer. Both ASPP and P-gp may be potential biomarkers in the treatment of cervical cancer.
RCT Entities:
PURPOSE: To evaluate the sensitivity of apoptosis-stimulating protein of p53 (ASPP) and P-glycoprotein (P-gp) to the recombinant human adenovirus-p53 (rAd-p53) combined with neoadjuvant chemotherapy for locally advanced cervical cancer and their predictive value for efficacy. METHODS: 80 patients with histopathologically diagnosed locally advanced cervical cancer (stage Ib2-IIa2) and operative treatment from February 2009 to June 2013 were enrolled and randomly divided into 3 groups: radical hysterectomy group (RH group, n=30), simple intravenous chemotherapy with cisplatinpaclitaxel group (TP group, n=30) and gene therapy + intravenous chemotherapy group with cisplatin+paclitaxel (rAd-p53 + TP group, n=20). Patients in the RH group were directly operated, those in the TP group were treated with TP chemotherapy for 2 courses, and those in the rAd-p53 + TP group were treated with the same chemotherapy regimen and the rAd-p53 agent (1×1012 virus particles) was injected for the first time 3 days after chemotherapy for 3 times. The changes in tumor volume, adverse reactions and survival of patients in the TP group and rAd-p53 + TP group, and the levels of p53, ASPP2, inhibitory member of the ASPP family (iASPP) and P-gp in postoperative tumor tissues in the 3 groups were evaluated. RESULTS: The efficacy was evaluated for all patients in the TP group and rAd-p53 + TP group 3 weeks after chemotherapy. The tumor was reduced by 10.90±2.62 cm2 after medication in the TP group and 15.25±4.01 cm2 after medication in rAd-p53 + TP group, and the difference was statistically significant. The response rate [complete response (CR) + partial response (PR)] was 76.7% in the TP group and 95% in the rAd-p53 + TP group, with statistically significant difference. The positive expression rate of p53 protein showed a gradual decreasing trend in the RH group, TP group and rAd-p53 + TP group, with statistically significant difference (p<0.05). The positive expression rate of ASPP2 displayed a gradual increasing trend in the RH group, TP group and rAd-p53 + TP group, without statistically significant difference (p>0.05). The positive expression rate of iASPP was different and gradually declined in the RH group, TP group and rAd-p53 + TP group (p<0.05). Moreover, the positive expression rate of P-gp was also different among the 3 groups, and it was increased in the TP group, while it was decreased in the RH and rAd-p53 + TP group (p<0.05). CONCLUSION: The intratumor injection of rAd-p53 into patients with cervical cancer is safe and effective, showing a new way in the gene therapy of cervical cancer. Both ASPP and P-gp may be potential biomarkers in the treatment of cervical cancer.