- Volume 15 Issue 8
DOI QR Code
Schedule-Dependent Effects of Kappa-Selenocarrageenan in Combination with Epirubicin on Hepatocellular Carcinoma
- Ji, Yu-Bin (Life Science and Environmental Science Research Center, Harbin University of Commerce) ;
- Ling, Na (Life Science and Environmental Science Research Center, Harbin University of Commerce) ;
- Zhou, Xiao-Jun (Department of Life Sciences, Luoyang Normal University) ;
- Mao, Yun-Xiang (College of Marine Life Sciences, Ocean University of China) ;
- Li, Wen-Lan (Life Science and Environmental Science Research Center, Harbin University of Commerce) ;
- Chen, Ning (Life Science and Environmental Science Research Center, Harbin University of Commerce)
- Published : 2014.04.30
Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.
- Wiangnon S, Kamsa-ard S, Suwanrungruang K, et al (2012). Trends in incidence of hepatocellular carcinoma, 1990-2009, Khon Kaen, Thailand. Asian Pac J Cancer Prev, 13, 1065-8. https://doi.org/10.7314/APJCP.2012.13.3.1065
- Zhu AX (2006). Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be? Oncologist, 11, 790-800. https://doi.org/10.1634/theoncologist.11-7-790
- Zhu WJ, Huang CY, Li C, et al (2013). Risk factors for early recurrence of HBV-related hepatocellular carcinoma meeting Milan criteria after curative resection. Asian Pac J Cancer Prev, 14, 7101-6. https://doi.org/10.7314/APJCP.2013.14.12.7101
- Wang W, Qin SK, Chen BA, et al (2001). Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma. World J Gastroenterol, 7, 702-5.
- Wei HL, Zhang ZW, Gao LP, et al (2006). Kappaselenocarrageenan overcomes apoptosis resistance in multidrug-resistant K562 /ADM cells by down-regulating expression of mdr1 gene and its product P-glycoprotein. J Mod Oncol, 14, 1489-92.
- Weinert T (1998). DNA damage and checkpoint pathways: molecular anatomy and interactions with repair. Cell, 94, 555-8. https://doi.org/10.1016/S0092-8674(00)81597-4
- Wrobel JK, Seelbach MJ, Chen L, et al (2013). Supplementation with selenium-enriched yeast attenuates brain metastatic growth. Nutr Cancer, 65, 563-70. https://doi.org/10.1080/01635581.2013.775315
- Wu X, Chen ZR, Zhang GJ (2004). Effective Composition of Kappa-selenocarrageenan Inducing Apoptosis of Osteosarcoma Cell Line. Fudan Univ J Med Sci, 31, 128-31.
- Yan PW, Huang XE, Jiang Y, et al (2010). Clinical comparison of safety and efficacy of vinorelbine/epirubicin (NE) with fluorouracil/epirubicin/cyclophosphamide (FEC). Asian Pac J Cancer Prev, 11, 1115-8.
- Yeo Y, Gwack J, Kang S, et al (2013). Viral hepatitis and liver cancer in Korea: an epidemiological perspective. Asian Pac J Cancer Prev, 14, 6227-31. https://doi.org/10.7314/APJCP.2013.14.11.6227
- Zekri AR, Hassan ZK, Bahnassy AA, et al (2012). Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus. Asian Pac J Cancer Prev, 13, 5433-8. https://doi.org/10.7314/APJCP.2012.13.11.5433
- Zhang ZW, Wei HL, Su HX (2005). Immunoregulatory and anti-tumor effects of kappa-selenocarrageenan. J Lanzhou Univ (Med Sci), 31, 88-91.
- Swanton C (2004). Cell-cycle targeted therapies. Lancet Oncol, 5, 27-36. https://doi.org/10.1016/S1470-2045(03)01321-4
- Nair R, Ramakrishnan G, Nair NN, et al (1998). A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-hodgkin’s lymphoma. Cancer, 82, 2282-8. https://doi.org/10.1002/(SICI)1097-0142(19980601)82:11<2282::AID-CNCR26>3.0.CO;2-P
- Norsa'adah B, Nurhazalini-Zayani CG (2013). Epidemiology and survival of hepatocellular carcinoma in north-east Peninsular Malaysia. Asian Pac J Cancer Prev, 14, 6955-9. https://doi.org/10.7314/APJCP.2013.14.11.6955
- Roché H, De Benedictis E, Cottura E, Govi S, et al (2012). A phase I study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer. Clin Breast Cancer, 12, 167-74. https://doi.org/10.1016/j.clbc.2012.03.009
- Unek IT, Unek T, Oztop I, et al (2012). Bimonthly regimen of high-dose leucovorin, infusional 5-fluorouracil, epirubicin and cisplatin (modified ECF) as adjuvant chemotherapy in resected gastric adenocarcinoma. Chemotherapy, 58, 233-40. https://doi.org/10.1159/000339493
- Vadgama JV, Wu YY, Shen D, Block J (2000). Effect of selenium in combination with adriamycin or taxol on several different cancer cells. Anticancer Res, 20, 1391-414.
- Vermeulen K, Van Bockstaele DR, Berneman ZN (2003) The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif, 36, 131-49. https://doi.org/10.1046/j.1365-2184.2003.00266.x
- Vici P, Brandi M, Giotta F, et al (2012). A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. Ann Oncol, 23, 1121-9. https://doi.org/10.1093/annonc/mdr412
- Wang L, Wang G, Yang D, et al (2013). Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression. Mol Med Rep, 8, 1279-85.
- Li SH, Guo ZX, Xiao CZ, et al (2013). Risk factors for early and late intrahepatic recurrence in patients with single hepatocellular carcinoma without macrovascular invasion after curative resection. Asian Pac J Cancer Prev, 14, 4759-63. https://doi.org/10.7314/APJCP.2013.14.8.4759
- Lener MR, Gupta S, Scott RJ, et al (2013). Can selenium levels act as a marker of colorectal cancer risk? BMC Cancer, 13, 214-9. https://doi.org/10.1186/1471-2407-13-214
Li F, Shi YZ (2000). Study of phase II clinical trial of
$\kappa$-selenocarrageenan in cancer patients. Chin J Clin Oncol, 27, 309-11.
- Li H, Hu Y, Li N, Zhou Y (2012). Liver fibrosis and five year survival of hepatocellular cancer cases undergoing transcatheter arterial chemo embolization using small doses. Asian Pac J Cancer Prev, 13, 1589-93. https://doi.org/10.7314/APJCP.2012.13.4.1589
- Liang T, Chen EQ, Tang H (2013). Hepatitis B virus gene mutations and hepatocarcinogenesis. Asian Pac J Cancer Prev, 14, 4509-13. https://doi.org/10.7314/APJCP.2013.14.8.4509
- Lim S, Kaldis P (2013). Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development, 140, 3079-93. https://doi.org/10.1242/dev.091744
- Lin ZJ, Wang Y (1993). Kappa-selenocarrageenan-A new type of organic selenium compounds. In: Lin Zheng-jie Trace element analysis and application. Tongji Medical University Publisher, Wuhan, 34-6.
- Ling N, Deng D, Ji YB (2009). Studies on biological effects of kappa-selenocarrageenan on human hepatocarcinoma HepG-2 cells. Asia-Pac Trad Med, 5, 14-6.
- Ling N (2012). Growth inhibition and cell cycle arrest of kappaselenocarrageenan and paclitaxel on HepG-2 cells. Adv Mater Res, 343-344, 530-4.
- Mao YM, Luo ZY, Li B, Hu TY (2012). Prospective study on the survival of HCC patients treated with transcatheter arterial lipiodol chemoembolization. Asian Pac J Cancer Prev, 13, 1039-42. https://doi.org/10.7314/APJCP.2012.13.3.1039
- He N, Shi X, Zhao Y, et al (2013). Inhibitory effects and molecular mechanisms of selenium-containing tea polysaccharides on human breast cancer MCF-7 cells. J Agric Food Chem, 61, 579-88. https://doi.org/10.1021/jf3036929
- Chen P, Hu MD, Deng XF, Li B (2013). Genistein reinforces the inhibitory effect of Cisplatin on liver cancer recurrence and metastasis after curative hepatectomy. Asian Pac J Cancer Prev, 14, 759-64. https://doi.org/10.7314/APJCP.2013.14.2.759
- Esposito L, Indovina P, Magnotti F, et al (2013). Anticancer therapeutic strategies based on CDK inhibitors. Curr Pharm Des, 19, 5327-32. https://doi.org/10.2174/13816128113199990377
- Findlay BP, Walker-Dilks C (1998). Epirubicin, alone or in combination chemotherapy, for metastatic breast cancer. Provincial Breast Cancer Disease Site Group and the Provincial Systemic Treatment Disease Site Group. Cancer Prev Control, 2, 140-6.
- Hu YJ, Chen Y, Zhang YQ, et al (1997). The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res, 56, 331-41. https://doi.org/10.1007/BF02785304
- Khasraw M, Bell R, Dang C (2012). Epirubicin: is it like doxorubicin in breast cancer? Breast, 21, 142-9. https://doi.org/10.1016/j.breast.2011.12.012
- Kong N, Zhang XM, Wang HT, et al (2013). Inhibition of growth and induction of differentiation of SMMC-7721 human hepatocellular carcinoma cells by oncostatin M. Asian Pacific J Cancer Prev, 14, 747-52. https://doi.org/10.7314/APJCP.2013.14.2.747
- Kryczyk J, Zagrodzki P (2013). Selenium in Graves’ disease. Postepy Hig Med Dosw (Online), 67, 491-8. https://doi.org/10.5604/17322693.1051000
- Launchbury AP, Habboubi N (1993). Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treat Rev, 19, 197-228. https://doi.org/10.1016/0305-7372(93)90036-Q
- Lee J, Park JO, Kim WS, et al (2004). Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma. Cancer Chemother Pharmacol, 54, 385-90. https://doi.org/10.1007/s00280-004-0837-7
- Bose P, Simmons GL, Grant S (2013). Cyclin-dependent kinase inhibitor therapy for hematologic malignancies. Expert Opin Investig Drugs, 22, 723-38. https://doi.org/10.1517/13543784.2013.789859
- Abou-Alfa GK, Johnson P, Knox JJ, et al (2010). Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA, 304, 2154-60. https://doi.org/10.1001/jama.2010.1672
- Alatise OI, Babalola OO, Omoniyi-Esan GO, et al (2013). Selenium levels in neoplastic breast lesions. Niger Postgrad Med J, 20, 91-7.
- Berk V, Kaplan MA, Tonyali O, et al (2013). Efficiency and side effects of sorafenib therapy for advanced hepatocellular carcinoma: a retrospective study by the anatolian society of medical oncology. Asian Pac J Cancer Prev, 14, 7367-9. https://doi.org/10.7314/APJCP.2013.14.12.7367
- Boulin M, Guiu S, Chauffert B, et al (2011). Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma. Anticancer Drugs, 22, 741-8. https://doi.org/10.1097/CAD.0b013e328346a0c5
- Bruyère C, Meijer L (2013). Targeting cyclin-dependent kinases in anti-neoplastic therapy. Curr Opin Cell Biol, 25, 772-9. https://doi.org/10.1016/j.ceb.2013.08.004
- Cao J, Huang XE, Liu J, et al (2013). Comparison of efficacy and toxicity of first line chemotherapy with or without epirubicin for patients with advanced stage soft tissue sarcoma. Asian Pac J Cancer Prev, 14, 7171-7. https://doi.org/10.7314/APJCP.2013.14.12.7171
- Coukell AJ, Faulds D (1997). Epirubicin. An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer. Drugs, 53, 453-82. https://doi.org/10.2165/00003495-199753030-00008
- Chen J, Yao Q, Li D, et al (2013). Neoadjuvant rhendostatin, docetaxel and epirubicin for breast cancer: efficacy and safety in a prospective, randomized, phase II study. BMC Cancer, 13, 248-54. https://doi.org/10.1186/1471-2407-13-248
- Solanum Nigrum Polysaccharide (SNL) Extract Effects in Transplanted Tumor-bearing Mice - Erythrocyte Membrane Fluidity and Blocking of Functions vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10469
- Mus81 knockdown improves chemosensitivity of hepatocellular carcinoma cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway vol.5, pp.2, 2015, https://doi.org/10.1002/cam4.588
- Thermosensitive folic acid-targeted poly (ethylene-co-vinyl alcohol) hemisuccinate polymeric nanoparticles for delivery of epirubicin to breast cancer cells vol.25, pp.11, 2016, https://doi.org/10.1007/s13726-016-0483-z