Modulation of chemosensitivity in human colon carcinoma cells by downregulating protein kinase C alpha expression.
Protein kinase C (PKC) is thought to play a role in tumor progression and drug resistance of colon carcinomas. Specifically, the PKC alpha 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 PKC alpha expression by transfecting human colon carcinoma cells with an antisense PKC alpha 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 PKC alpha expression vector (but not antisense PKC beta 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 PKC alpha expression vector. This stably transfected cell line, which expressed a high level of antisense PKC alpha RNA with a concurrent reduction of PKC alpha protein expression, was found to exhibit an increased sensitivity to these anticancer drugs. Thus, strategies designed to downregulate PKC alpha expression may have potential in improving the responses of colon carcinoma cells to cytotoxic drugs.
Chakrabarty
S
S
Division of Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Huang
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S
D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000096:biosynthesis*; D051571:Protein Kinase C-alpha; D016372:RNA, Antisense / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016372:RNA, Antisense; D012334:RNA, Neoplasm; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha