The inhibitory effect of cisplatin in combination with irradiation on lung tumor cell growth is due to induction of tumor cell apoptosis.
Chemoradiation is becoming an important method of treatment of advanced lung cancer. Although many studies have demonstrated the efficacy of chemoradiation against lung tumors, the mechanism of its effect is still poorly understood. In this study, we analyzed the combined effect of cisplatin (CDDP) and irradiation on human lung cancer cell lines (PC-9 and Lu 134A) in vitro using MTT assay and isobologram analysis. To study whether the combined effect is due to induction of tumor cell apoptosis, we further quantified the nuclear fragmentation of tumor cells by flow cytometric analysis. Our study revealed that a combination of cisplatin and irradiation had an additive inhibitory effect on both PC-9 (adenocarcinoma) and Lu 134A (small cell carcinoma) tumor cell growth. Cisplatin improved the sensitivity of tumor cells to irradiation. The use of both cisplatin and irradiation doses could be reduced without decreasing the inhibitory effect. The additive inhibitory effect was correlated positively with the levels of tumor cell nuclear fragmentation. We concluded that combination treatment with cisplatin and irradiation is effective against lung tumors, not only small cell carcinoma but also non-small cell carcinoma, and the inhibitory effect was due to induction of tumor cell apoptosis.
Fujita
M
M
Third Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Fujita
T
T
Kodama
T
T
Tsuchida
T
T
Higashino
K
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000532:radiotherapy*; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin