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Prediction of Chemotherapeutic Response in Unresectable Non-small-cell Lung Cancer (NSCLC) Patients by 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) Assay

  • Chen, Juan (Department of Pharmacy, The Affiliated Cancer Hospital of Guangzhou Medical College) ;
  • Cheng, Guo-Hua (College of Pharmacy, Jinan University) ;
  • Chen, Li-Pai (Department of Gynecology, The Affiliated Cancer Hospital of Guangzhou Medical College) ;
  • Pang, Ting-Yuan (Department of Pharmacy, The Affiliated Cancer Hospital of Guangzhou Medical College) ;
  • Wang, Xiao-Le (Department of Pharmacy, The Affiliated Cancer Hospital of Guangzhou Medical College)
  • Published : 2013.05.30

Abstract

Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.

Keywords

Chemosensitivity;chemotherapeutic agents;MTS assay;non-small cell lung cancer

References

  1. Arias JL (2011). Drug targeting strategies in cancer treatment: an overview. Mini Rev Med Chem, 11, 1-17. https://doi.org/10.2174/138955711793564024
  2. Baggstrom MQ, Stinchcombe TE, Fried DB, et al (2007). Third-generation chemotherapy agents in the treatment of advanced non-small cell lung cancer: a meta-analysis. J Thorac Oncol, 2, 845-53. https://doi.org/10.1097/JTO.0b013e31814617a2
  3. Berg K, Zhai L, Chen M, Kharazmi A, Owen TC (1994). The use of a water-soluble formazan complex to quantitate the cell number and mitochondrial function of Leishmania major promastigotes. Parasitol Res, 80, 235-9. https://doi.org/10.1007/BF00932680
  4. Buttke TM, McCubrey JA,Owen TC (1993). Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines. J Immunol Methods, 157, 233-40. https://doi.org/10.1016/0022-1759(93)90092-L
  5. Chang AY, Wang M (2013). In-vitro growth inhibition of chemotherapy and molecular targeted agents in hepatocellular carcinoma. Anticancer Drugs, 24, 251-9. https://doi.org/10.1097/CAD.0b013e32835ba289
  6. Chao D, Bahl P, Houlbrook S, et al (1999). Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay. Br J Cancer, 81, 1280-4. https://doi.org/10.1038/sj.bjc.6694366
  7. Domingues PM, Zylberberg R, da Matta de Castro T, Baldotto CS,de Lima Araujo LH (2013). Survival data in elderly patients with locally advanced non-small cell lung cancer. Med Oncol, 30, 449. https://doi.org/10.1007/s12032-012-0449-8
  8. Fujita Y, Hiramatsu M, Kawai M, et al (2009). Histoculture drug response assay predicts the postoperative prognosis of patients with esophageal cancer. Oncol Rep, 21, 499-505.
  9. Han M, Liu Q, Yu J, Zheng S (2010). Identification of candidate molecular markers predicting chemotherapy resistance in non-small cell lung cancer. Clin Chem Lab Med, 48, 863-7. https://doi.org/10.1515/cclm.2010.169
  10. Higashiyama M, Kodama K, Yokouchi H, et al (2001). Cisplatin-based chemotherapy for postoperative recurrence in non-small cell lung cancer patients: relation of the in vitro chemosensitive test to clinical response. Oncol Rep, 8, 279-83.
  11. Higashiyama M, Oda K, Okami J, et al (2010). Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients. Lung Cancer, 68, 472-7. https://doi.org/10.1016/j.lungcan.2009.07.005
  12. Higashiyama M, Okami J, Maeda J, et al (2012). Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST). J Thorac Dis, 4, 40-7.
  13. Inal A, Kaplan MA, Kucukoner, et al (2012). Cisplatin-based therapy for the treatment of elderly patients with nonsmall-cell lung cancer: a retrospective analysis of a single institution. Asian Pacific J Cancer Prev, 13, 1837-40. https://doi.org/10.7314/APJCP.2012.13.5.1837
  14. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  15. Kawamura M, Gika M, Abiko T, et al (2007). Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST). Cancer Chemother Pharmacol, 59, 507-13. https://doi.org/10.1007/s00280-006-0292-8
  16. Khabar KS, al-Zoghaibi F, Dzimiri M, et al (1996). MTS interferon assay: a simplified cellular dehydrogenase assay for interferon activity using a water-soluble tetrazolium salt. J Interferon Cytokine Res, 16, 31-3. https://doi.org/10.1089/jir.1996.16.31
  17. Lee KH, Lee KY, Jeon YJ, et al (2012). Gefitinib in selected patients with pre-treated non-small-cell lung cancer: results from a phase IV, multicenter, non-randomized study (SELINE). Tuberc Respir Dis (Seoul), 73, 303-11. https://doi.org/10.4046/trd.2012.73.6.303
  18. Li XD, Han JC, Zhang YJ, Li HB, Wu XY (2013). Common variations of DNA repair genes are associated with response to platinum-based chemotherapy in NSCLCs. Asian Pacific J Cancer Prev, 14, 145-8. https://doi.org/10.7314/APJCP.2013.14.1.145
  19. Malich G, Markovic B,Winder C (1997). The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines. Toxicology, 124, 179-92. https://doi.org/10.1016/S0300-483X(97)00151-0
  20. Mercer SJ, Somers SS, Knight LA, et al (2003). Heterogeneity of chemosensitivity of esophageal and gastric carcinoma. Anticancer Drugs, 14, 397-403. https://doi.org/10.1097/00001813-200307000-00002
  21. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981). Reporting results of cancer treatment. Cancer, 47, 207-14. https://doi.org/10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6
  22. Mohammed Ael S, Eguchi H, Wada S, et al (2012). TMEM158 and FBLP1 as novel marker genes of cisplatin sensitivity in non-small cell lung cancer cells. Exp Lung Res, 38, 463-74. https://doi.org/10.3109/01902148.2012.731625
  23. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  24. Noguchi K, Iwahashi M, Tani M, et al (2005). Evaluation of chemosensitivity testing with highly purified tumor cells in 435 patients with gastric carcinoma using an MTT assay. Anticancer Res, 25, 931-7.
  25. O'Toole SA, Sheppard BL, McGuinness E, Gleeson NC, Bonnar J (2001). Serous papillary adenocarcinomas of the ovary display heterogeneity in their response to chemotherapy. Int J Gynecol Cancer, 11, 365-71. https://doi.org/10.1046/j.1525-1438.2001.01041.x
  26. O'Toole SA, Sheppard BL, McGuinness EP, et al (2003). The MTS assay as an indicator of chemosensitivity/resistance in malignant gynaecological tumours. Cancer Detect Prev, 27, 47-54. https://doi.org/10.1016/S0361-090X(02)00171-X
  27. Ozols RF, Willson JK, Grotzinger KR, Young RC (1980). Cloning of human ovarian cancer cells in soft agar from malignant and peritoneal washings. Cancer Res, 40, 2743-7.
  28. Rotter BA, Thompson BK, Clarkin S, Owen TC (1993). Rapid colorimetric bioassay for screening of Fusarium mycotoxins. Nat Toxins, 1, 303-7. https://doi.org/10.1002/nt.2620010509
  29. Sedlakova I, Laco J, Tosner J, et al (2012). [Proteins of resistence and drug resistence in ovarian carcinoma patients]. Klin Onkol, 25, 457-63.
  30. Sofian ZM, Abdullah JM, Rahim AA, et al (2012). Cytotoxicity evaluation of vancomycin and its complex with betacyclodextrin on human glial cell line. Pak J Pharm Sci, 25, 831-7.
  31. van Meerloo J, Kaspers GJ, Cloos J (2011). Cell sensitivity assays: the MTT assay. Methods Mol Biol, 731, 237-45. https://doi.org/10.1007/978-1-61779-080-5_20
  32. Wu B, Zhu JS, Zhang Y, Shen WM, Zhang Q (2008). Predictive value of MTT assay as an in vitro chemosensitivity testing for gastric cancer: one institution's experience. World J Gastroenterol, 14, 3064-8. https://doi.org/10.3748/wjg.14.3064
  33. Yoshimasu T, Oura S, Hirai I, et al (2007). Data acquisition for the histoculture drug response assay in lung cancer. J Thorac Cardiovasc Surg, 133, 303-8. https://doi.org/10.1016/j.jtcvs.2006.06.030
  34. Zubor P, Kajo K, Stanclova A, et al (2008). Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma. Eur J Cancer Prev, 17, 33-8. https://doi.org/10.1097/CEJ.0b013e3280145e4b

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