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，共培养了30个人肺癌细胞系和5个其他细胞系。用四甲基偶氮唑盐比色法检测长春新碱与吲哚美辛(2μg/ml)作用72小时后细胞的存活情况。平均调节活性(MI)在腺癌为2.91，鳞癌为1.92，大细胞癌为3.06，小细胞癌为1.67。用放射免疫法测定65株肺癌细胞株培养上清液中NSE和CEA的水平。小细胞肺癌和非小细胞肺癌的NSE平均值分别为30[-+]22 ng/ml和9.1[-+]8.7 ng/ml(p&lt；0.001)。CEA在小细胞肺癌和非小细胞肺癌中的平均值分别为14.4[-+]20.6 ng/ml和32.3[-+]80.3 ng/ml。在每一个SC…中，NSE和CEA的产量之间存在显著的负相关更多的LS细胞系(r=-0.42，p&lt；0.05)。在小细胞肺癌细胞系中，细胞的增殖能力和体外生长特性与NSE和CEA水平相关。3)采用四甲基偶氮唑盐比色法检测了吲哚美辛对4株化疗后复发的大细胞样变异型小细胞肺癌细胞株和6株悬浮集落或神经细胞型小细胞肺癌细胞株VCR和MTX的调节作用。用长春新碱和甲氨蝶呤加或不加消炎痛(2μg/ml)处理72小时，观察细胞的存活情况。变异小细胞肺癌细胞对VCR的抑制指数显著高于经典单纯小细胞肺癌细胞(p&lt；4)近期对2例常规化疗后复发的IV期小细胞肺癌患者采用长春新碱、甲氨蝶呤、吲哚美辛联合调理治疗，两例患者均在一周期内基本达到CR，且门诊未见明显不良反应。5)我们证明消炎痛与环孢菌素A联用对体外培养的人肺癌细胞VCR细胞毒有明显的协同调节作用。(结论)认为消炎痛对多种人肺癌细胞VCR的调变活性是一种普遍的效应，与长春新碱联合应用对人肺癌细胞株VCR活性的调变具有普遍意义。MTX联合消炎痛可能是治疗常规化疗后复发的IV期小细胞肺癌的有效方法。较少

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