Synergistic interaction between melittin and chemotherapeutic agents and their possible mechanisms: an experimental research / 中国中西医结合杂志

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms.</p><p><b>METHODS</b>Median effect analysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC-823 cells with or without treatment were measured by real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>(1) Both melittin and chemotherapeutic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT + melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta-tubulin III (TUBB3), and microtubule-associated protein tau (MAPT).</p><p><b>CONCLUSIONS</b>Melittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might be associated with down-regulating chemotherapeutic agent-associated genes.</p>