Clark S, McGuckin M A, Hurst T, Ward B G
Department of Obstetrics and Gynaecology, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
Cancer Immunol Immunother. 1994 Aug;39(2):100-4. doi: 10.1007/BF01525315.
This study aimed to investigate whether the biological response modifiers (BRM) interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN gamma was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.
本研究旨在调查生物反应调节剂(BRM)γ干扰素(IFNγ)和肿瘤坏死因子α(TNFα)是否能在体外增强顺铂对卵巢肿瘤细胞的细胞毒性作用。通过放射性标记的胸腺嘧啶核苷掺入试验检测了四种细胞系(OAW42、GG、JAM和PE01)对药物及药物组合的敏感性。细胞系对顺铂及每种BRM的固有细胞毒性作用表现出一定范围的敏感性。当IFNγ与顺铂联合使用时,四种细胞系中的三种出现了顺铂毒性的显著增强。TNFα在两种细胞系中表现出这种作用,但在一种细胞系中降低了顺铂的毒性。这些药物的纯粹相加作用可能解释了某些情况下顺铂毒性增强的现象。然而,至少在一种细胞系(PEO1)中,TNFα和IFNγ均与顺铂表现出明显的协同作用。这些BRM与顺铂联合使用,对于某些卵巢癌患者可能比单独使用顺铂提供更好的抗肿瘤方案,但患者之间的反应可能存在异质性。