Modulation of chemosensitivity in human colon carcinoma cells by downregulating Protein Kinase Cα expression

Protein kinase C (PKC) is thought to play a role in tumor progression and drug resistance of colon carcinomas. Specifically, the PKCα isoform has been implicated in drug resistance and responsiveness of colon carcinoma cells to growth factors. Therefore, in this study we determined the effect of downregulating PKCα expression by transfecting human colon carcinoma cells with an antisense PKCα expression vector and then determined the sensitivity of these cells to the anticancer drugs mitomycin C (MMC), 5-fluorouracil (5-FU) and vincristine (Vin). Transiently transfecting the human colon carcinoma cell lines Moser, SW480 and HT29 with antisense PKCα expression vector (but not antisense PKCβ expression vector) consistently increased the sensitivity of these cells to MMC, 5-FU and VIN by several-fold. Sensitivity to these drugs was then further determined in the Moser colon carcinoma cell line stably transfected with antisense PKCα expression vector. This stably transfected cell line, which expressed a high level of antisense PKCα RNA with a concurrent reduction of PKCα protein expression, was found to exhibit an increased sensitivity to these anticancer drugs. Thus, strategies designed to downregulate PKCα expression may have potential in improving the responses of colon carcinoma cells to cytotoxic drugs.