Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer

Diagnostic Pathology

Ying-Chun Yin¹  Yong-Cheng Cao¹  Ming Geng¹  Pei-Feng Li¹  Lin Wang¹ 

[1] Department of Pathology, General Hospital of Jinan Military Command, 250031, Jinan, Shandong Province, China

关键词: MTT assay;    hTERT mRNA;    Chemosensitivity;    Anticancer drugs;    Gastric cancer;   

Others  :  807463
DOI  :  10.1186/1746-1596-8-33

 received in 2012-12-20, accepted in 2013-01-30,  发布年份 2013

【 摘 要 】

Background

The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them.

Methods

The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization.

Results

Taxol, Cisplatin and 5-Fluorouracil were in general more effective than Adriamycin and Mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-Fluorouracil or Adriamycin in GC.

Conclusions

These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483 webcite

【 授权许可】

   
2013 Wang et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Hamajima N, Naito M, Kondo T, Goto Y: Genetic factors involved in the development of Helicobacter pylori-related gastric cancer. Cancer Sci 2006, 97(11):1129-1138.
• [2]Nagini S: Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 2012, 4(7):156-169.
• [3]Chipponi J, Huguier M, Pezet D, Basso N, Hay JM, Quandalle P, Jaeck D, Fagniez PL, Gainant A: Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer. Am J Surg 2004, 187(3):440-445.
• [4]Field K, Michael M, Leong T: Locally advanced and metastatic gastric cancer: current management and new treatment developments. Drugs 2008, 68(3):299-317.
• [5]Ma BB, Hui EP, Mok TS: Population-based differences in treatment outcome following anticancer drug therapies. Lancet Oncol 2010, 11(1):75-84.
• [6]Li Y, Huang W, Huang S, Du J, Huang C: Screening of anti-cancer agent using zebrafish: comparison with the MTT assay. Biochem Biophys Res Commun 2012, 422(1):85-90.
• [7]Stockert JC, Blazquez-Castro A, Canete M, Horobin RW, Villanueva A: MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem 2012, 114(8):785-796.
• [8]Nakamura R, Saikawa Y, Kubota T, Kumagai A, Kiyota T, Ohashi M, Yoshida M, Otani Y, Kumai K, Kitajima M: Role of the MTT chemosensitivity test in the prognosis of gastric cancer patients after postoperative adjuvant chemotherapy. Anticancer Res 2006, 26(2B):1433-1437.
• [9]Sexton AN, Youmans DT, Collins K: Specificity requirements for human telomere protein interaction with telomerase holoenzyme. J Biol Chem 2012, 287(41):34455-34464.
• [10]Lundblad V: Telomere end processing: unexpected complexity at the end game. Genes Dev 2012, 26(11):1123-1127.
• [11]Liu H, Liu S, Wang H, Xie X, Chen X, Zhang X, Zhang Y: Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer. Diagn Pathol 2012, 7:147. BioMed Central Full Text
• [12]Rubtsova MP, Vasilkova DP, Malyavko AN, Naraikina YV, Zvereva MI, Dontsova OA: Telomere lengthening and other functions of telomerase. Acta Naturae 2012, 4(2):44-61.
• [13]Shay JW, Wright WE: Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 2005, 26(5):867-874.
• [14]Frias C, Pampalona J, Genesca A, Tusell L: Telomere dysfunction and genome instability. Front Biosci 2012, 17:2181-2196.
• [15]Ozer H, Yenicesu G, Arici S, Cetin M, Tuncer E, Cetin A: Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors. Diagn Pathol 2012, 7:124. BioMed Central Full Text
• [16]Liu Y, Dong XL, Tian C, Liu HG: Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx. Diagn Pathol 2012, 7:34. BioMed Central Full Text
• [17]Nowak J, Januszkiewicz D, Lewandowski K, Nowicka-Kujawska K, Pernak M, Rembowska J, Nowak T, Wysocki J: Activity and expression of human telomerase in normal and malignant cells in gastric and colon cancer patients. Eur J Gastroenterol Hepatol 2003, 15(1):75-80.
• [18]Chen KY, Lee LN, Yu CJ, Lee YC, Kuo SH, Yang PC: Elevation of telomerase activity positively correlates to poor prognosis of patients with non-small cell lung cancer. Cancer Lett 2006, 240(1):148-156.
• [19]Yang SM, Fang DC, Yang JL, Chen L, Luo YH, Liang GP: Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro. Eur J Cancer Prev 2008, 17(3):209-217.
• [20]Safont MJ, Gil M, Sirera R, Jantus-Lewintre E, Sanmartin E, Gallach S, Caballero C, Del Pozo N, Palomares E, Camps C: The prognostic value of hTERT expression levels in advanced-stage colorectal cancer patients: a comparison between tissue and serum expression. Clin Transl Oncol 2011, 13(6):396-400.
• [21]Ishikawa T, Kamiyama M, Hisatomi H, Ichikawa Y, Momiyama N, Hamaguchi Y, Hasegawa S, Narita T, Shimada H: Telomerase enzyme activity and RNA expression in adriamycin-resistant human breast carcinoma MCF-7 cells. Cancer Lett 1999, 141(1–2):187-194.
• [22]Smith V, Dai F, Spitz M, Peters GJ, Fiebig HH, Hussain A, Burger AM: Telomerase activity and telomere length in human tumor cells with acquired resistance to anticancer agents. J Chemother 2009, 21(5):542-549.
• [23]Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65(1–2):55-63.
• [24]Suzuki T, Ochiai T, Nakajima K, Matsubara H, Arima M, Hori S, Hayashi H, Shimada H, Takeda A, Yanagawa T, Sen K: A feasibility study of chemosensitivity assay by adhesive tumor cell culture system using biopsy specimens for gastric cancer. J Surg Oncol 2000, 74(2):141-147.
• [25]Andric Z, Randjelovic T, Kovcin V, Gutovic J, Crevar S, Murtezani Z, Kostic S: Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer. Srp Arh Celok Lek 2012, 140(5–6):305-312.
• [26]Sakamoto J, Matsui T, Kodera Y: Paclitaxel chemotherapy for the treatment of gastric cancer. Gastric Cancer 2009, 12(2):69-78.
• [27]Jimenez P, Pathak A, Phan AT: The role of taxanes in the management of gastroesphageal cancer. J Gastrointest Oncol 2011, 2(4):240-249.
• [28]Park SH, Kim YS, Hong J, Park J, Nam E, Cho EK, Shin DB, Lee JH, Lee WK, Chung M: Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study. Anticancer Drugs 2008, 19(3):303-307.
• [29]Kyo S, Inoue M: Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy? Oncogene 2002, 21(4):688-697.
• [30]Liu JP: Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J 1999, 13(15):2091-2104.
• [31]Li W, Li L, Liu Z, Liu C, Straat K, Bjorkholm M, Jia J, Xu D: Expression of the full-length telomerase reverse transcriptase (hTERT) transcript in both malignant and normal gastric tissues. Cancer Lett 2008, 260(1–2):28-36.
• [32]Cerni C: Telomeres, telomerase, and myc. An update. Mutat Res 2000, 462(1):31-47.
• [33]Sakin V, Eskiocak U, Kars MD, Iseri OD, Gunduz U: hTERT gene expression levels and telomerase activity in drug resistant MCF-7 cells. Exp Oncol 2008, 30(3):202-205.