Expression of connexin 43 in ovarian cancer and its relationship with chemoresistance

Abstract

To examine the expression of protein kinase C (PKC), connexin 43 (Cx43) and non-phosphorylated Cx43 in ovarian cancer, and discuss the role of phosphorylated of Cx43 in chemoresistance in ovarian cancer. We examined the expression of Cx43, non-phosphorylated Cx43 and PKC in ovarian cancer tissue by immunohistochemistry, and compared their expression in chemosensitivity group and chemoresistance group. Cisplatin resistant ovarian cancer cell line SKOV3/DDP cells were treated by staurosporine (a kind of PKC inhibitors). Then expression of Cx43, nonphosphorylated Cx43 and PKC were tested. Meanwhile, we tested chemosensitivity of SKOV3/DDP cells by ATP bioluminescence tumor chemosensitivity assay (ATP-TCA). (1) Immunohistochemically, the rates of positive expression of Cx43 and non-phosphorylated Cx43 were 54%, 14% respectively in the chemoresistance group, which were 83%, 59% in the chemosensitivity group respectively (P < 0.05). The rate of positive expression of PKC in 28 chemoresistance ovarian cancer cases (64%) was higher than that in 29 chemosensitivity cases (31%, P < 0.05). Both of them were significantly lower in chemoresistance group than in chemosensitivity group (P < 0.05). In addition, the expression of PKC was negatively correlated with the expression of Cx43 and non-phosphorylated Cx43. The correlation coefficients were -0.626 and -0.714, respectively (P < 0.05). (2) Immunohistochemically, PKC was down regulated, and Cx43 and non-phosphorylated Cx43 were up regulated in SKOV3/DDP cells after staurosporine treatment. The longer the staurosporine worked, the more expression of Cx43 was. (3) By ATP-TCA, SKOV3/DDP cells were resistant to paclitaxel and cisplatin. The tumor growth inhibition was higher in the group of paclitaxel or cisplatin combined staurosporine than in the group of paclitaxel or cisplatin alone. The sensitivity was intermediate in the group combined with low concentration staurosporine (1 x 10(-8) mol/L), and the sensitivity was high in the group combined with high concentration staurosporine (1 x 10(-7) mol/L). Phosphorylation of Cx43 caused by PKC leads to decrease in the expression of Cx43. This effect makes ovarian cancer cells less chemosensitive. Phosphorylation of Cx43 caused by PKC can be inhibited by staurosporine.