Osteopontin Gene Expression is Inversely Regulate 5-Fluorouracil Drug Resistance in Colon Cancer
Cancer Research Journal
Volume 3, Issue 2, March 2015, Pages: 42-46
Received: Mar. 28, 2015;
Accepted: Apr. 15, 2015;
Published: Apr. 27, 2015
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Go Nakajima, Department of Chemotherapy and Palliative Care, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo, Japan
Kazuhiko Hayashi, Department of Chemotherapy and Palliative Care, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo, Japan
Masakazu Yamamoto, Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo, Japan
Background: Resistance to chemotherapeutic drugs complicates the treatment of cancer patients. The extracellular matrix protein osteopontin (OPN) plays multiple roles in the proliferation and metastasis of cancer cells. We therefore attempted to determine whether OPN expression correlated with drug resistance. Methods: OPN expression in the HCT 116 colon cancer cell line was inhibited by an OPN-short interfering RNA (siRNA). We determined the cytotoxic effect (IC50) of 5-fluorouracil (5FU) on these cells. Patients with recurrence or colorectal cancer or harbored residual tumor cells were treated with S-1-based chemotherapy. The levels of OPN mRNA expression in the tumors were determined and compared with the patients’ responses to chemotherapy. Results: The IC50 of 5FU for HCT 116 cells transfected with the OPN-siRNA was 32.9 μM. In contrast, the IC50 values for cells transfected with a negative control siRNA, mock-transfected cells, or untreated cells were 6.58 μM, 7.08 μM, and 6.76 μM, respectively (P<0.001). The level of OPN mRNA expression in the S-1 non-responder group was significantly lower than that of the responder group (P = 0.0387). Survival analysis revealed no significant difference between the responder and non-responder groups (P = 0.8737). Conclusions: The level of OPN expression plays a role in the resistance of colorectal tumor cells to 5FU.
Osteopontin Gene Expression is Inversely Regulate 5-Fluorouracil Drug Resistance in Colon Cancer, Cancer Research Journal.
Vol. 3, No. 2,
2015, pp. 42-46.
T. Matsuda, T. Marugame, K. Kamo, K. Katanoda, W. Ajiki, T. Sobue, et al., "Cancer incidence and incidence rates in Japan in 2002: based on data from 11 population-based cancer registries," Jpn J Clin Oncol, vol. 38, pp. 641-8, Sep 2008.
J. Ferlay, H. R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008," Int J Cancer, vol. 127, pp. 2893-917, Dec 2010.
C. Tournigand, T. André, E. Achille, G. Lledo, M. Flesh, D. Mery-Mignard, et al., "FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study," J Clin Oncol, vol. 22, pp. 229-37, Jan 2004.
J. Cassidy, S. Clarke, E. Díaz-Rubio, W. Scheithauer, A. Figer, R. Wong, et al., "Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer," J Clin Oncol, vol. 26, pp. 2006-12, Apr 2008.
Y. Yamada, D. Takahari, H. Matsumoto, H. Baba, M. Nakamura, K. Yoshida, et al., "Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial," Lancet Oncol, vol. 14, pp. 1278-86, Dec 2013.
H. S. Hochster, L. L. Hart, R. K. Ramanathan, B. H. Childs, J. D. Hainsworth, A. L. Cohn, et al., "Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study," J Clin Oncol, vol. 26, pp. 3523-9, Jul 2008.
H. Hurwitz, L. Fehrenbacher, W. Novotny, T. Cartwright, J. Hainsworth, W. Heim, et al., "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer," N Engl J Med, vol. 350, pp. 2335-42, Jun 2004.
D. Cunningham, Y. Humblet, S. Siena, D. Khayat, H. Bleiberg, A. Santoro, et al., "Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer," N Engl J Med, vol. 351, pp. 337-45, Jul 2004.
C. HEIDELBERGER, N. K. CHAUDHURI, P. DANNEBERG, D. MOOREN, L. GRIESBACH, R. DUSCHINSKY, et al., "Fluorinated pyrimidines, a new class of tumour-inhibitory compounds," Nature, vol. 179, pp. 663-6, Mar 1957.
H. Okada, K. Moriwaki, R. Kalluri, T. Takenaka, H. Imai, S. Ban, et al., "Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats," Am J Physiol Renal Physiol, vol. 278, pp. F110-21, Jan 2000.
M. Mazzali, T. Kipari, V. Ophascharoensuk, J. A. Wesson, R. Johnson, and J. Hughes, "Osteopontin--a molecule for all seasons," QJM, vol. 95, pp. 3-13, Jan 2002.
J. Zhang, K. Takahashi, F. Takahashi, K. Shimizu, F. Ohshita, Y. Kameda, et al., "Differential osteopontin expression in lung cancer," Cancer Lett, vol. 171, pp. 215-22, Oct 2001.
A. B. Tuck and A. F. Chambers, "The role of osteopontin in breast cancer: clinical and experimental studies," J Mammary Gland Biol Neoplasia, vol. 6, pp. 419-29, Oct 2001.
D. X. Cao, Z. J. Li, X. O. Jiang, Y. L. Lum, E. Khin, N. P. Lee, et al., "Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers," World J Gastroenterol, vol. 18, pp. 3923-30, Aug 2012.
K. A. Brakora, H. Lee, R. Yusuf, L. Sullivan, A. Harris, T. Colella, et al., "Utility of osteopontin as a biomarker in recurrent epithelial ovarian cancer," Gynecol Oncol, vol. 93, pp. 361-5, May 2004.
G. F. Weber, "The metastasis gene osteopontin: a candidate target for cancer therapy," Biochim Biophys Acta, vol. 1552, pp. 61-85, Dec 2001.
M. K. El-Tanani, "Role of osteopontin in cellular signaling and metastatic phenotype," Front Biosci, vol. 13, pp. 4276-84, 2008.
H. Rangaswami, A. Bulbule, and G. C. Kundu, "Osteopontin: role in cell signaling and cancer progression," Trends Cell Biol, vol. 16, pp. 79-87, Feb 2006.
A. Bellahcène, V. Castronovo, K. U. Ogbureke, L. W. Fisher, and N. S. Fedarko, "Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer," Nat Rev Cancer, vol. 8, pp. 212-26, Mar 2008.
J. L. Lee, M. J. Wang, P. R. Sudhir, G. D. Chen, C. W. Chi, and J. Y. Chen, "Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN-CD44V interaction enhances survival in gastrointestinal cancer cells," Cancer Res, vol. 67, pp. 2089-97, Mar 2007.
Z. S. Chen and A. K. Tiwari, "Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases," FEBS J, vol. 278, pp. 3226-45, Sep 2011.
M. M. Gottesman, "Mechanisms of cancer drug resistance," Annu Rev Med, vol. 53, pp. 615-27, 2002.
M. R. Lackner, T. R. Wilson, and J. Settleman, "Mechanisms of acquired resistance to targeted cancer therapies," Future Oncol, vol. 8, pp. 999-1014, Aug 2012.
D. B. Longley, D. P. Harkin, and P. G. Johnston, "5-fluorouracil: mechanisms of action and clinical strategies," Nat Rev Cancer, vol. 3, pp. 330-8, May 2003.
D. Salonga, K. D. Danenberg, M. Johnson, R. Metzger, S. Groshen, D. D. Tsao-Wei, et al., "Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase," Clin Cancer Res, vol. 6, pp. 1322-7, Apr 2000.
A. Angelucci, C. Festuccia, G. L. Gravina, P. Muzi, L. Bonghi, C. Vicentini, et al., "Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells," Prostate, vol. 59, pp. 157-66, May 2004.
T. Standal, M. Borset, and A. Sundan, "Role of osteopontin in adhesion, migration, cell survival and bone remodeling," Exp Oncol, vol. 26, pp. 179-84, Sep 2004.
P. Y. Wai and P. C. Kuo, "Osteopontin: regulation in tumor metastasis," Cancer Metastasis Rev, vol. 27, pp. 103-18, Mar 2008.
G. F. Weber, G. S. Lett, and N. C. Haubein, "Osteopontin is a marker for cancer aggressiveness and patient survival," Br J Cancer, vol. 103, pp. 861-9, Sep 2010.