摘要
Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovirus carrying the wild-type PTEN gene （Ad-PTEN）. RL95-2 cells, an endometrial carcinoma cell line lacking PTEN function, was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin, decreased proliferation rate, and elevated apoptosis and Go/G1 arrest. Furthermore, the tumorigenicity of these cells was also completely suppressed. These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection, induce apoptosis of tumor cells, and reduce expression of proliferating cell nuclear antigen （PCNA）. Immunohistochemistry analysis also showed that the expression of progesterone receptors （PR） in Ad-PTEN treated tumor cells were induced, while P-glycoproteins （P-gp） and estrogen receptors （ER） decreased significantly. Conclusion： PTEN may play an important role in the development of endometrial carcinoma. Our findings cast new lights for treatment ofendometrial carcinoma.
Objective:To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma.Methods and Results:We constructed recombinant adenovirus carrying the wild-type PTEN gene(Ad-PTEN).RL95-2 cells,an endometrial carcinoma cell line lacking PTEN function,was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin,decreased proliferation rate,and elevated apoptosis and G0/G1 arrest.Furthermore,the tumorigenicity of these cells was also completely suppressed.These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection,induce apoptosis of tumor cells,and reduce expression of proliferating cell nuclear antigen(PCNA).Immunohistochemistry analysis also showed that the expression of progesterone receptors(PR) in Ad-PTEN treated tumor cells were induced,while P-glycoproteins(P-gp) and estrogen receptors(ER) decreased significantly.Conclusion:PTEN may play an important role in the development of endometrial carcinoma.Our findings cast new lights for treatment of endometrial carcinoma.
基金
Supported by the National Natural Science Foundation of China(30471676)
Shanghai Science and Technology Committee(04DZ19207-2)
