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11种化疗药物对卵巢癌细胞的抑制作用及其有核细胞细胞毒性研究

Study on the inhibition of 11 kinds of chemotherapeutic drugs in the ovarian cancer cells and the cytotoxicity in peripheral blood karyocyte

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【作者】 唐东平陈心秋唐凯张洁清贺海平

【Author】 Tang Dong-Ping Chen Xin-Qiu Tang Kai et al Department of Tumor Research Institute of Guangxi, Nanning 530021, China

【机构】 广西壮族自治区肿瘤防治研究所

【摘要】 目的:为了进一步提高临床卵巢癌患者的化学药物治疗效率,观察11种化疗药物体外对卵巢癌患者癌细胞的杀伤作用,及其外周血有核细胞(白细胞、淋巴细胞和粒细胞)的毒性效应并探讨其可能存在的相关性及可行性。方法:采用经典的MTT比色法分别进行体外药物敏感性试验及细胞毒性试验,检测34例住本院卵巢癌患者经手术切下新鲜肿瘤组织标本(经病理检查证实)的癌细胞对11种临床常用化疗药物:紫杉醇(TXL)、威猛(VM-26)、阿霉素(ADM)、长春新碱(VCR)、平阳霉素(PYM)、顺铂(DDP)、环磷酰胺 (CTX)、足叶乙甙(VP-16)、健择(GEM)、草酸铂(OXA)、吡柔比星(THP)的敏感性和其药物对外周血有核细胞中的白细胞、淋巴细胞、粒细胞(术后2周内恢复期)的细胞毒性。试验药物浓度按照各药血浆峰值作统一倍数稀释。所有数据用统计学软件分析。结果:各药物对癌细胞抑制率的差异有显著性。其中,TXL和VM-26两种化疗药物:对卵巢癌细胞的抑制率均达到30%以上,可认为属于卵巢癌细胞的敏感药物;其余9种药物对卵巢癌细胞的抑制率均较低。在敏感性程度上,白细胞和粒细胞的敏感性更接近于癌细胞的敏感性,各药物对每种细胞的抑制率唯有对癌细胞与粒细胞的细胞毒性作用有相关性(rs=0.7136,P<0.05),而癌细胞与白细胞、癌细胞与淋巴细胞的细胞毒性作用均无相关性。癌细胞对VCR的敏感率低于白细胞、淋巴细胞和粒细胞对其药物的敏感率;癌细胞对CTX的敏感率低于淋巴细胞对其药物的敏感率;癌细胞对VP-16的敏感率低于粒细胞对其药物的敏感率(细胞对药物的抑制率统一作≥30%以上计算)。结论:紫杉醇和VM一26两种化疗药物属于卵巢癌细胞敏感药物;这些药物对卵巢癌的疗效与其对粒细胞的毒性显著相关;在没能进行肿瘤细胞药敏试验检测的情况下,卵巢癌患者的化疗以外周血粒细胞细胞毒性的检测替补癌细胞药敏试验的检测更为可行,并能为临床扩大优化个体化疗方案提供实用而有参考价值的实验依据。

【Abstract】 Objective: To improve the curative effect of chemotherapeutic drugs in the ovarian cancer ,we studied the the lethal effect of 11 kinds of anticancer drugs in the ovarian cancer cells and the cytotoxicity in peripheral blood karyocytes (leucocytes, lymphocytes and granulocytes),and investigate the feasibility and relativity of the two effects. Methods: The tumor chemosensitivity test and the cytotoxicity test in vitro were respectively carried out by the classic MTT colorimetric assay to detect the sensitivity of 11 kinds of anticancer drugs including TXL 、VM-26 、ADM 、VCR 、PYM 、DDP 、CTX 、VP-16 、GEM 、OXA 、THP in the tumor cells of 34 cases with ovarian cancer( which can be confirmed by pathology), and to detect the cytotoxicity of these drugs in leucocytes, lymphocytes and granulocytes(convalescence stage of postop. in two weeks).The density of the drugs were all multiple diluted according to themselves crest value density in blood plasma.All data were statistical analysised by the software. Results: There were significant differences of inhibition rates of the above-mentioned drugs in the tumor cells.The inhibition rates of TXL and VM-26 all achieved above 30% in the ovarian cancer cells, so they were sensitive drugs of the ovarian cancer cells; the inhibition rates of the other drugs were all lower.The sensitivity of leucocytes and granulocytes were close to the cancer cells’ .There was relativity between the inhibition rates of the above-mentioned drugs in the tumor cells and the cytotoxicity in granulocytes (rs=0.7136,P<0.05),but this relativity was not available between the the tumor cells’ and the leucocytes’ ,and not available between the the tumor cells’ and the lymphocytes’ also.The sensitive rates of VCR in cancer cells were lower than leucocytes’, lymphocytes’ and granulocytes’; The sensitive rates of CTX in cancer cells were lower than lymphocytes’; The sensitive rates of VP-16 in cancer cells were lower than granulocytes’ (which were calculated according to the all cells’ inhibition ratio ≥30%). Conclusion: The ovarian cancer cells were sensitivity to TXL and VM-26; There was evident relativity about the all anticancer drugs between the therapeutic effect and the cytotoxicity in granulocytes.These results prompt that the cytotoxicity test of the peripheral blood karyocytes may take the place of the chemosensitivity test of tumor cells for reference to choosing chemotherapeutic drugs when there was not sufficient experiment condition,and it can provid practical and valuable reference for expanding to optimize the individual treatment in ovarian cancer chemotherapy.

  • 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
  • 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
  • 【会议时间】2006-10
  • 【会议地点】中国天津
  • 【分类号】R737.31
  • 【主办单位】中国抗癌协会、中华医学会肿瘤学分会
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