Study on Biochemical Modulation Therapy for Drug Resistant SCLS

1)用30株人肺癌细胞系和5株其它细胞系研究了吲哚美辛对长春新碱的调节作用。MTT法检测VCR联合或不联合吲哚美辛（2μg/ml）处理72 h后细胞的存活率。腺癌、鳞癌、大细胞癌和小细胞癌的平均调节活性（MI）分别为2.91、1.92、3.06和1.67。2）采用放射免疫分析法（RIA）测定65株肺癌细胞培养上清中NSE和CEA的含量。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<0.001）。小细胞肺癌和非小细胞肺癌的CEA平均值分别为14.4 ± 20.6ng/ml和32.3 ± 80.3ng/ml。各SC中NSE和CEA的表达呈显著的负相关 ...更多信息 LS细胞株的凋亡率（r=-0.42，p<0.05）。在SCLC细胞系中，细胞增殖能力和体外生长特性与NSE和CEA水平相关。3）采用MTT法检测吲哚美辛对4株化疗后复发的SCLC大细胞样变异细胞系和6株SCLC纯细胞系中VCR和MTX的调节作用。用VCR和MTX加或不加吲哚美辛（2μg/ml）处理这些细胞系72小时，检测其存活率。变异SCLC细胞中VCR的MI显著高于经典纯SCLC细胞（p<0.05）4）近期对2例IV期小细胞肺癌常规化疗后复发患者采用VCR、MTX、消炎痛联合调整治疗，两例患者仅在一个周期的调整治疗中就达到了几乎完全缓解，在门诊没有明显的不良反应。5）我们证明，联合使用吲哚美辛和环孢菌素A揭示了一个强大的协同调节作用，VCR细胞毒性在体外人肺癌细胞。（结论）吲哚美辛对VCR的调节作用是多种肿瘤细胞的普遍效应，VCR、MTX和吲哚美辛联合应用对IV期SCLC化疗后复发有较好的治疗效果。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