The effects of activation and inhibition agents of protein kinase C on the function and expression of P-glycoprotein in drug-resistant gastric cancer cells / 中华消化杂志

ABSTRACT

Objective To study the effects of activation and inhibition agents of protein kinase C on the function and expression of P glycoprotein in drug resistant gastric cancer cells. Methods Immunohistochemical staining and FACS were used to determine the expression of P glycoprotein on drug resistant gastric cancer cells SGC7901/VCR and its parent cells SGC7901, which were treated or not treated by activation or inhibition agents of protein kinase C(PMA or H 7). Double labeled immunoflurescent and laser scan confocal microscopy were used to detect the coexpression of protein kinase C ? and P glycoprotein on drug resistant gastric cancer cells. Rohdamin 123 was used as fluorescent probe to observe the effects of PMA and H 7 on the function of P glycoprotein and drug accumulation in SGC7901/VCR. Results P glycoprotein had positive staining on SGC7901 cells and much stronger staining on SGC7901/VCR cells. Protein kinase C ? and P glycoprotein exhibited coexpression on SGC7901 cells and much higher coexpression level on SGC7901/VCR cells. When treated by PMA, SGC7901/VCR cells showed time dependent decreasing of drug accumulation, enhancing function and decreasing expression of P glycoprotein. When treated by H 7, SGC7901/VCR cells showed time dependent increasing of drug accumulation, weakening function and increasing expression of P glycoprotein.Conclusion Protein kinase C may play a role in multidrug resistance of gastric cancer cells via modulating the expression and function of P glycoprotein.