抗癌药物与钙拮抗剂合用对体外人胃癌细胞的影响

Effect of combined use chemotherapeutic agents and calcium antagonists on human gastric cancer cell lines in vitro

目的和方法：本文报道了抗癌药物与５－氟脲嘧啶（５－ＦＵ）、阿霉素（ＤＯＸ）及长春新碱（ＶＣＲ）与钙拮抗剂维拉帕米（ＶＰＭ）、尼卡地平（ＮＩＣ）、汉防已甲素（ＴＥＴ）、硝苯吡啶（ＮＩＦ）及硫氮草酮（ＤＩＬ）单独和联合应用对体外人胃癌细胞株ＭＫＮ４５、ＭＫＮ２８及ＭＧＣ８０３细胞增殖影响的研究结果。结果：不同浓度的５种钙拮抗剂单独处理各胃癌细胞株，发现随着浓度升高，胃癌细胞增殖受到的抑制作用也增强，其中ＶＰＭ、ＮＩＣ和ＴＥＴ较为显著。在联合用药实验中，无毒剂量ＶＰＭ、ＮＩＣ与低浓度ＤＯＸ、５－ＦＵ、ＶＣＲ合用时，可使这些化疗药物抑制胃癌细胞增殖的作用增强２．７～７．５倍。小剂量的ＴＥＴ可增强ＤＯＸ对３种胃癌细胞株的细胞毒作用，亦可增强ＶＣＲ、５－ＦＵ对某些细胞株的作用。而ＮＩＦ和ＤＩＬ对抗癌药物细胞毒性的增强作用不显著。结论：结果提示ＶＰＭ、ＮＩＣ及ＴＥＴ等钙拮抗剂能增强ＤＯＸ。

Aim and Methods:The effects of anticancer drugs such as 5-fluorouraci(5-FU),doxorubicin(DOX) and vincristine(VCR) used alone or in combination with calcium antagonists (CAs) such as verapamil(VPM),nicardipine(NIC), Tetrandine(tet), nifidipine(NIF) and diltiazem(DIL) on the proliferation of human gastic cancer cell lines (MKN45,MKN28 and MGC803) were studied in vitro.Results:An inhibition of proliferation on the tumor cell lines in culture was observed when treated separately with five different concentration,in particular VPM,NIC or TET.The response of tumor to CAs was related to the dose adiminstered. In the experiments of combinated use of cytotoxic drugs and CAs,for MKN45,MKN28 and MGC803 cells,the addition of VPM,NIC in dose which,when used alone,had little effect on cell lines would significantly increase the effect of DOX,5-FU and VCR to a degree 2.7 to 7.5-folds.By the addition of TET in lowdose,a significant potentiation of DOX cytotoxicity was found to all tumour cell lines,and the sensitivity of some tumor cells to VCR or 5-FU tended to be increased as well.NIF or DIL rarely significant enhanced the cytotoxicity of these antineoplastic agents on 3 gastric cancer cell lines.Conclusions:The results indicate that CAs(VPM,NIC or TET) can enhance antitumor activity of some chemotherapeutic agents like 5-FU,DOX and VCR against human gastric cancer cell line in vitro and may be used as an potentiator for these anticancer drugs in vivo.