Study on Biochemical Modulation Therapy for Drug Resistant SCLS

1)研究了吲哚美辛对长春新碱的调节作用。用MTT法观察加吲哚美辛（2μg/ml）或不加吲哚美辛（2μg/ml）的VCR处理细胞72 h后的存活率。腺癌的平均调节活性（MI）为2.91，鳞状细胞癌为1.92，大细胞癌为3.06，小细胞癌为1.67。其他肿瘤细胞系显示VCR和吲哚美辛的联合作用。2)用放射免疫法（RIA）测定65株肺癌细胞株培养上清液中NSE和CEA的含量。SCLC和非SCLC患者NSE平均值分别为30【负加】22 ng/ml和9.1【负加】8.7 ng/ml （p<0.001）。CEA在SCLC和非SCLC中的平均值分别为14.4【负正】20.6 ng/ml和32.3【负正】80.3 ng/ml。各SC…More LS细胞系NSE与CEA产量呈显著的反比相关（r=-0.42, p<0.05）。在SCLC细胞系中，细胞体外增殖能力和生长特性与NSE和CEA水平相关。NSE水平与预后有显著相关性（p<0.05）。3)采用MTT法检测吲哚美辛对4例化疗后复发肿瘤大细胞样变异型SCLC细胞株和6例漂浮集落型和神经细胞型SCLC纯细胞株VCR和MTX的调节作用。分别用VCR和MTX （2μg/ml）加或不加吲哚美辛（2μg/ml）处理这些细胞株72小时，观察其存活率。变异SCLC细胞VCR的MI值明显高于经典SCLC纯细胞（p<0.05）。4)近期，对2例经普通化疗后复发的IV期SCLC患者联合VCR、MTX、吲哚美辛进行了调节治疗，两例患者在门诊仅用一个周期的调节治疗即可基本达到CR，且无明显不良反应。5)研究表明，吲哚美辛和环孢素A联合使用对体外人肺癌细胞的VCR细胞毒性具有明显的协同调节作用。（结论）认为吲哚美辛对VCR的调节活性是对人类各种癌细胞的普遍作用，VCR、MTX、吲哚美辛联合调节治疗可能是普通化疗后复发的IV期SCLC的有效治疗方法。少

1) The modulating activity of indomethacin to vincristine was investigated in thirty human pulmonary carcinoma cell lines and five other cell lines. The survival of these cell lines treated with VCR with or without indomethacin (2μg/ml) for 72 hours were examined using MTT assay. Mean modulating activity (MI) was 2.91 in adenocarcinomas, 1.92 in squamous cell carcinomas, 3.06 in large cell carcinomas and 1.67 in small cell carcinomas. Other tumors cell lines showed the potent combined effect of VCR and indomethacin.2) NSE and CEA levels in the culture supernatant of 65 pulmonary carcinoma cell lines were measured by a radioimmunoassay (RIA). The mean value of NSE was 30 【minus-plus】 22 ng/ml and 9.1 【minus-plus】 8.7 ng/ml in SCLC and non-SCLC, respectively (p<0.001). The mean value of CEA was 14.4 【minus-plus】 20.6 ng/ml and 32.3 【minus-plus】 80.3 ng/ml in SCLC and non-SCLC, respectively. There was a significant inverse proportional correlation between NSE and CEA production in each SC … More LS cell lines (r=-0.42, p<0.05). In the SCLC lines, cell proliferation ability and growth characteristic in vitro had correlation with NSE and CEA levels. There was significant correlation between NSE levels and their prognosis (p<0.05).3) We examined the modulating effect of indomethacin for VCR and MTX in 4 large cell like variant SCLC cell lines originated from tumors which recurred after chemotherapy and 6 pure SCLC cell lines with floating colony type or neurocyte type sing MTT assay. The survival of these cell lines treated with VCR and MTX with or without indomethacin (2μg/ml) for 72 hours were examined. The MI for VCR in variant SCLC cells were significantly high as compared those of classical pure SCLC cells (p<0.05).4) Recently, the modulation therapy combined with VCR, MTX and indomethacin was treated for 2 patients with stage IV SCLC recurred after ordinary chemotherapy, and both of the patients achieved almost CR in only one cycle of the modulation therapy without obvious adverse effects at outpatient clinic.5) We demonstrate that combined use of indomethacin and cyclosporin A reveal a potent synergistic modulation effect to VCR cytotoxicity in human lung carcinoma cells in vitro.(Conclusion) It is considered that modulating activity of indomethacin for VCR is a general effect for various human cancer cells, and that modulation therapy combined with VCR, MTX and indomethacin may be an effective treatment for the stage IV SCLC recurred after ordinary chemotherapy. Less