Sensitization of SiHa cell to gemcitabine by CD40 activation and its overexpression in cervical carcinoma

Abstract

CD40, a member of the tumor necrosis factor receptor superfamily, is widely expressed on various cell types. Some studies show that CD40 expression is related to several carcinomas, where its function remains largely unknown. This study investigated the expression of CD40 on cervical carcinoma and evaluated the effect of agnostic anti-CD40 mAb (5C11) on tumor cell line (SiHa). CD40 expression on the primary cervical carcinoma samples was detected by immunohistochemistry. Results showed that CD40 is commonly expressed in human cervical carcinoma, which is higher than that of normal cervix, cervical precancerous tissue and chronic cervicitis. Treatment of the SiHa cell with the agonistic anti-CD40 monoclonal antibody or Gemcitabine alone did not inhibit the proliferation of the SiHa cell in vitro, but the activation of CD40 on SiHa could enhance its sensitivity to Gemcitabine. Furthermore, CD40 activation blocked SiHa in the S phase, stimulated proapoptotic Bax and inhibited antiapoptotic Bcl-XL mRNA synthesis in the SiHa cell. Apoptosis in SiHa was associated with an increasing ratio of Bax to Bcl-XL in mRNA levels. It is concluded that use of the anti-CD40 mAb 5C11 in combination with chemotherapy may have significant therapeutic potential.