Differences in effects of oncogenes on sensitivity to anticancer drugs.
Methods to predict the responsiveness of a particular tumor to a particular anticancer drug are desirable not only for chemotherapy but also for chemoradiotherapy. Here, we examined the effects of viral or activated oncogenes on sensitivity to anticancer drugs by using SHOK (Syrian hamster Osaka-Kanazawa) cells and their transfectants. The IC50 of each transfectant was compared with that of the pSV2Neo transfected control. Cells transfected with the c-myc, v-mos, or v-fgr gene increased their sensitivity to bleomycin, while those transfected with the H-ras gene developed resistance. Resistance to cisplatin was conferred by the introduction of the H-ras or c-cot gene. In the case of adriamycin, the c-myc or c-cot transfectant increased sensitivity and the H-ras transfectant decreased it. Mitomycin C resistance was observed by the introduction of the K-ras gene. Thus, the H-ras gene was found to be involved in the development of resistance to three of the four anticancer drugs. In addition, we have for the first time shown that mos and cot have an effect on sensitivity to three and all of the four anticancer drugs, respectively. These results suggest that the expression of each oncogene would differently affect sensitivity to the four anticancer drugs used in this study, and this property could be a possible marker to predict chemosensitivity.
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Tomoyuki
T
Hamamoto
Keiji
K
Suzuki
Hitoshi
H
Sasaki
Masataka
M
Ichikawa
Seiji
S
Kodama
Masami
M
Watanabe
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation / Q000187:drug effects*; D007928:Lethal Dose 50; D008647:Mesocricetus; D015513:Oncogene Proteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D015513:Oncogene Proteins