Zeng-Rong N, Paterson J, Alpert L, Tsao M S, Viallet J, Alaoui-Jamali M A
Department of Pathology, Sir Mortimer Jewish General Hospital, Montreal, Quebec, Canada.
Cancer Res. 1995 Nov 1;55(21):4760-4.
Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and established cell lines were examined and compared to SCLC cell lines established previously from untreated patients. The overall DNA repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was determined for cisplatin in vitro. N-SCLC cells were found to be significantly more resistant to cisplatin than SCLC cell lines isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC cells originating from patients who were untreated previously (P < 0.05). Correlation was also observed between chloramphenicol acetyltransferase activity and intrinsic resistance to cisplatin. However, no significant difference was observed between primary N-SCLC cultures and established cell lines. This study indicates that elevated DNA repair capacity is associated with drug resistance in lung cancer and suggests that modulation of DNA repair mechanism(s), such as the incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may help to improve therapeutic strategies of N-SCLC.
与小细胞肺癌（SCLC）不同，非小细胞肺癌（N-SCLC）即使在未接受过药物治疗的情况下通常也对化疗无反应，而小细胞肺癌最初对化疗有反应。这种内在抗性的机制尚不清楚。本研究旨在探讨DNA修复在N-SCLC对顺铂内在抗性中的作用。检测了一组原发性N-SCLC细胞培养物和已建立的细胞系，并与先前从未经治疗的患者建立的SCLC细胞系进行比较。通过细胞重新激活被顺铂损伤的pRSV-CAT质粒的能力（“宿主细胞重新激活”试验）来估计总体DNA修复能力。测定了顺铂在体外的细胞毒性。发现N-SCLC细胞比从未经治疗的患者分离出的SCLC细胞系对顺铂的抗性明显更高（P<0.01）。N-SCLC细胞重新激活被顺铂损伤并转染到细胞中的pRSV-CAT质粒的能力在N-SCLC细胞中高于从未经治疗的患者来源的SCLC细胞（P<0.05）。还观察到氯霉素乙酰转移酶活性与对顺铂的内在抗性之间的相关性。然而，在原发性N-SCLC培养物和已建立的细胞系之间未观察到显著差异。本研究表明，DNA修复能力的提高与肺癌的耐药性相关，并表明调节DNA修复机制，如在治疗方案中加入特定的DNA修复抑制剂，可能有助于改善N-SCLC的治疗策略。
