[Basic Research of the Adenovirus-mediated hCTR1 Transfection on the Treatment of Cisplatin Resistant Cervical Cancer].

OBJECTIVE

To induce cisplatin-resistant cervical squamous carcinoma cell line and investigate the drug resistant mechanisms and adenovirus trans-gene therapeutical treatment.

METHODS

The cisplatin-resistant subline,designated C-33A/cis,was originated by growing parental C-33A cells with gradually increasing doses of cisplatin. The cytotoxicity of cisplatin was determined by CCK-8 assay,and the CTR1 expression was measured by Western blot. Subcutaneous xenograft cervical tumor model was established by cisplatin-resistant C-33A/cis cell line. Recombinant adenovirus ad-hCTR1 was transfected into tumor by intratumoral injection and combined with cisplatin chemotherapy. The changes in the volume of tumor were observed and the mice were executed at 10th day after the last injection,and the expression of CTR1 in tumor tissues was detected by immunohistochemistry.

RESULTS

Cisplatin-resistant cervical carcinoma C-33A/cis cells were successfully induced by gradually increased concentration of cisplatin. The cytotoxic IC50 value of cisplatin on C-33A/cis had been upgraded from (1.86±0.08) to (8.11±0.21) μmol/L,while the CTR1 was found decreased by Western blot assay. Immunohistochemical analysis indicated that CTR1 expression was increased by intratumoral injection of adenovirus ad-hCTR1, and the tumor growth of C-33A/cis drug-resistant cervical carcinoma xenograft was inhibited by ad-hCTR1 transfection combined with cisplatin.

CONCLUSION

The combination therapy of ad-hCTR1 transfection and cisplatin was effective to inhibit the growth of drug-resistant C-33A/cis tumor.