Objective To predict clinical chemotherapy sensitivity of primary non-small cell lung cancer（NSCLC） by methylthiazal （MTT） tumor chemosensitivity assay method in vitro and detection of multidrug resistance gene1 （MDR1）, and provide reference for clinical individualized treatment. Methods We selected 80 fresh primary NSCLC samples from NSCLC patients who underwent surgical resection in Zibo Central Hospital Affiliated to Binzhou Medical College between January 2009 and December 2011. There were 46 male patients and 34 female patients with their median age of 54 （29 to 81）years. Viable NSCLC cells obtained from malignant tissue were tested for their sensitivity to cisplatin （DDP）, gemcitabine （GEM）, docetaxe （DOC）, etoposide （VP-16） ,and vinorelbine （NVB） using MTT assay in vitro. Fluorescent quantitative reverse transcriptase-polymerase chain reaction （RT-PCR） was used to analysis the expression level of multidrug resistance gene1 （MDR1）. Results After exposure to antitumor drugs, morphologic changes, decrease of metabolic activity, and apoptosis were detected in NSCLC cells. MTT results showed that different individual cancer cells had different chemosensitivity to antitumor drugs, and cancer cells also had different chemosensitivity to different antitumor drugs. Inhibitory rates of cancer cells exposed to DOC, GEM, and VP-16 were significantly higher than those of cancer cells exposed to DDP and NVB （42.5%±9.5%, 40.5%±6.5%, 38.4%±7.6% versus 31.5%±8.5%，32.5%±7.8%, P＜0.05）.
The positive rate of MDR1 in tumor tissues was 40.0% （32/80）. The expression of MDR1 was not associated with tumor histological type, degree of differentiation, lymph node metastasis and TNM stage. The expression of MDR1 was associated with resistance to NVB （χ2=5.209，P=0.022），GEM （χ2=4.769，P=0.029），VP-16 （χ2=4.596，P=0.032），and DDP（χ2=6.086，P=0.014）, but not associated with resistance to DOC（χ2=0.430，P=0.512）. Conclusion MTT chemosensitivity assay can effectively predict clinical chemotherapy sensitivity. Detection of MDR1, together with MTT chemosensitivity assay, can more accurately predict NSCLC chemosensitivity and be a guide for individualized chemotherapy of NSCLC.
Citation：
YIN Yingchun,WANG Xinmei,WANG Xinyun,HAN Hongmei,HOU Zhenbo,ZHANG Baohua,ZHANG Rimin.. Predicting Clinical Chemosensitivity of Non-small Cell Lung Cancer Using Methylthiazal Assay Combined with Detection of Multidrug Resistance Gene 1. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(5): 547-550. doi:
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Copyright © the editorial department of Chinese Journal of Clinical Thoracic and Cardiovascular Surgery of West China Medical Publisher. All rights reserved
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姚丽鸽，李鹏，张阳.GP方案与DP方案同期放化疗治疗局部晚期非小细胞肺癌的临床观察. 中国实用医刊，2011，38 （4）：97-98.
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Kitada K， Yamasaki T. The MDR1/ABCB1 regional amplification in large inverted repeats with asymmetric sequences and microhomologies at the junction sites. Cancer Genet Cytogenet， 2007， 178 （2）：120-127.
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Mizatani T， Masuda M， Nakai E， et al. Genuine functions of P-glycoprotein （ABCB1）.Curt Drug Metab， 2008， 9 （2）：167-174.
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Trussardi-Regnier A， Millot JM， Gorisse MC， et al. Detection of drug-resistance genes using single bronchoscopy biopsy specimens. Oncol Rep， 2007， 18 （3）：703-708.
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El-Kareh AW， Labes RE， Secomb TW. Cell cycle checkpoint models for cellular pharmacology of paclitaxel and platinum drugs. AAPS J， 2008，10 （1）：15-34.
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- 1. 姚丽鸽，李鹏，张阳.GP方案与DP方案同期放化疗治疗局部晚期非小细胞肺癌的临床观察. 中国实用医刊，2011，38 （4）：97-98.
- 2. Korpanty G， Smyth E， Carney DN. Update on anti-angiogenic therapy in non-small cell lung cancer：Are we making progress? J Thorac Dis， 2011， 3 （1）：19-29.
- 3. Alberg AJ， Ford JG， Samet JM， et al. Epidemiology of lung cancer：ACCP evidence-based clinical practice guidelines （2nd edition）. Chest， 2007， 132 （3 Suppl）：29S-55S.
- 4. 王磊， 侯生才， 李辉， 等. 血清肝细胞生长因子及转化生长因子-β水平在非小细胞肺癌患者术前分期中的意义. 中国胸心血管外科临床杂志， 2010， 17 （6）：462-466.
- 5. Srewart DT. Host factors that may limit efficacy of chemotherapy in non-small cell， small cell lung cancer. Crit Rev Oncol Hematol， 2010， 75 （3）：173-234.
- 6. Neubauer H， Stefanova M， Solomayer E， et al. Predicting resistance to platinum-containing chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer. Anticancer Res， 2008， 28 （2A）：949-955.
- 7. 赵丹， 吴令英， 王小兵， 等. 三磷酸腺苷-肿瘤体外药敏实验在预测原发性卵巢上皮性癌化疗敏感性中的应用价值. 中华肿瘤杂志， 2010， 32 （5）：368-372.
- 8. 耿明， 尹迎春， 曹永成， 等. 化疗药物对原代胃癌细胞的体外杀伤效应及其与端粒酶逆转录酶mRNA表达的关系. 中华肿瘤杂志， 2007， 29 （11）：838-841.
- 9. Douillard JY， Siena S， Cassidy J， et al. Randomized， phase III trial of panitumumab with infusional fluorouracil， leucovorin， and oxaliplatin （FOLFOX4） versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer：the PRIME study. J Clin Oncol， 2010， 28 （31）：4697-4705.
- 10. Cao W， Yang W， Lou G， et al. Phase Ⅱtrial of infusional flurouracil， leucovorin， oxaliplatin， and irinotecan （FOLFOXIRI）as first-line treatment for advanced gastric cancer. Anticancer Drugs， 2009， 20 （4）：287-293.
- 11. Stewart DT. Host factors that may limit efficacy of chemotherapy in non-small cell， small cell lung cancer. Crit Rev Oncol Hematol， 2010， 75 （3）：173-234.
- 12. Shervington A，Lu C.Expression of multidrug resistance genes in normal and cancer stem cells.Cancer Invest，2008，26 （5）：535-542.
- 13. Kitada K， Yamasaki T. The MDR1/ABCB1 regional amplification in large inverted repeats with asymmetric sequences and microhomologies at the junction sites. Cancer Genet Cytogenet， 2007， 178 （2）：120-127.
- 14. Roy S， Kenny E， Kennedy S， et al. MDR1/P-glycoprotein and MRP-1 mRNA and protein expression in non-small cell lung cancer. Anticancer Res， 2007， 27 （3A）：1325-1330.
- 15. Mizatani T， Masuda M， Nakai E， et al. Genuine functions of P-glycoprotein （ABCB1）.Curt Drug Metab， 2008， 9 （2）：167-174.
- 16. Palumbo R， Galvez BG， Pusterla T， et al. Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation. J Cell Biol， 2007， 179 （1）：33-40.
- 17. Trussardi-Regnier A， Millot JM， Gorisse MC， et al. Detection of drug-resistance genes using single bronchoscopy biopsy specimens. Oncol Rep， 2007， 18 （3）：703-708.
- 18. El-Kareh AW， Labes RE， Secomb TW. Cell cycle checkpoint models for cellular pharmacology of paclitaxel and platinum drugs. AAPS J， 2008，10 （1）：15-34.
- 19. Belani CP.Optimizing chemotherapy for advanced non-small cell lung Cancer：focus on docetaxel.Lung Cancer，2005， 50 （Suppl 2）：S3-S8.
- 20. Ramalingam S. First-line chemotherapy for advanced-stage non-small-cell lung cancer：focus on docetaxel. Clin Lung Cancer， 2005， 7 （Suppl 3）：S77-S82.
