Effects of Vitamin K2 Plus 5-Fluorouracil on Proliferation,Migration,and Invasiveness of Hepatocellular Carcinoma Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENGKang-wen ,  WANGGui-he , LUPeng-yun

Department of Gastroenterological Surgery, Tongling People's Hospital, Tongling 244000, Anhui Province, China;

Corresponding?author：

WANGGui-he, Email: yiyuanckw@163.com

Keywords：

Hepatocellular carcinoma; Vitamin K2; 5-fluorouracil; Chemotherapy protocol

DOI：

10.7507/1007-9424.20160339

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate effects of vitamin K2 in combination with 5-fluorouracil (5-FU) on proliferation, migration, and invasiveness of hepatocellular carcinoma cells in vitro. Methods Human hepatocellular carcinoma PLC/RAF/5 cells were cultured in vitro and exposed to vitamin K2 (10 μmol/L) and 5-FU (10 μg/mL) alone or in combination for 24 h. The cell proliferation, migration, and invasiveness were measured by CCK-8 assay, wound-scratch assay, and Matrigel invasion chamber assay, respectively. Results The abilities of proliferation, migration, and invasion of PLC/RAF/5 cells were significantly decreased after either alone vitamin K2 or 5-FU treatment (all P<0.05) as compared with the control cells, and above effects were further enhanced by the vitamin K2 in combination with 5-FU treatment as compared with either alone drug treatment (all P<0.05). Conclusion Combination use of vitamin K2 and 5-FU might be an effective method for inhibiting growth, migration, and invasiveness of hepatocellular carcinoma cells.

Citation： CHENGKang-wen, WANGGui-he, LUPeng-yun. Effects of Vitamin K2 Plus 5-Fluorouracil on Proliferation,Migration,and Invasiveness of Hepatocellular Carcinoma Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(11): 1321-1324. doi: 10.7507/1007-9424.20160339 Copy

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2.	Hasegawa K, Makuuchi M, Takayama T, et al. Surgical resection vs. percutaneous ablation for hepatocellular carcinoma:a preliminary report of the Japanese nationwide survey. J Hepatol, 2008, 49(4):589-594.
3.	Lord R, Suddle A, Ross PJ. Emerging strategies in the treatment of advanced hepatocellular carcinoma:The role of targeted therapies. Int J Clin Pract, 2011, 65(2):182-188.
4.	程康文, 李琪, 詹勇強, 等. 5-氟尿嘧啶對肝癌細胞株PLC/RAF/5生物學特性及耐藥機制的影響. 臨床肝膽病雜志, 2015, 31(9):1458-1463.
5.	Beulens JW, Booth SL, van den Heuvel EG, et al. The role of mena-quinones (vitamin K2) in human health. Br J Nutr, 2013, 110(8):1357-1368.
6.	Hitomi M, Yokoyama F, Kita Y, et al. Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo. Int J Oncol, 2005, 26(3):713-720.
7.	Yamamoto T, Nakamura H, Liu W, et al. Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K2. J Gastroenterol, 2009, 44(3):228-235.
8.	Zhong JH, Ke Y, Gong WF, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg, 2014, 260(2):329-340.
9.	Intaraprasong P, Siramolpiwat S, Vilaichone RK. Advances in management of hepatocellular carcinoma. Asian Pac J Cancer Prev, 2016, 17(8):3697-3703.
10.	Hirokawa F, Hayashi M, Miyamoto Y, et al. Outcomes and predic-tors of microvascular invasion of solitary hepatocellular carcinoma. Hepatol Res, 2014, 44(8):846-853.
11.	Zhong JH, Ma L, Li LQ. Postoperative therapy options for hepato-cellular carcinoma. Scand J Gastroenterol, 2014, 49(6):649-661.
12.	European Association for Study of Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. Eur J Cancer, 2012, 48(5):599-641.
13.	Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma for Asia. J Clin Oncol, 2013, 31(28):3501-3508.
14.	Kaseb AO, Shindoh J, Patt YZ, et al. Modified cisplatin/inter-feronα-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma. Cancer, 2013, 119(18):3334-3342.
15.	代景友, 楊樹萌, 張新晨, 等. 抑制自噬對5-氟尿嘧啶治療肝癌療效的影響及機制研究. 中國普外基礎與臨床雜志, 2013, 20(8):872-877.
16.	Wu J, Hu D, Zhang R. Depletion of Bmi-1 enhances 5-fluorouracil-induced apoptosis and autophagy in hepatocellular carcinoma cells. Oncol Lett, 2012, 4(4):723-726.
17.	Zhang H, Ozaki I, Hamajima H, et al. Vitamin K2 augments 5-fluo-rouracil-induced growth inhibition of human hepatocellular carci-noma cells by inhibiting NF-κB activation. Oncol Rep, 2011, 25(1):159-166.
18.	Otsuka M, Kato N, Shao RX, et al. Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Hepatology, 2004, 40(1):243-251.
19.	Azuma K, Urano T, Ouchi Y, et al. Vitamin K2 suppresses prolifera-tion and motility of hepatocellular carcinoma cells by activating steroid and xenobiotic receptor. Endocr J, 2009, 56(7):843-849.
20.	Xia J, Matsuhashi S, Hamajima H, et al. The role of PKC isoforms in the inhibition of NF-κB activation by vitamin K2 in human hepato-cellular carcinoma cells. J Nutr Biochem, 2012, 23(12):1668-1675.
21.	Li L, Qi Z, Qian J, et al. Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway. Mol Cell Biochem, 2010, 342(1-2):125-131.

1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, 2012, 142(6):1264-1273.
2. Hasegawa K, Makuuchi M, Takayama T, et al. Surgical resection vs. percutaneous ablation for hepatocellular carcinoma:a preliminary report of the Japanese nationwide survey. J Hepatol, 2008, 49(4):589-594.
3. Lord R, Suddle A, Ross PJ. Emerging strategies in the treatment of advanced hepatocellular carcinoma:The role of targeted therapies. Int J Clin Pract, 2011, 65(2):182-188.
4. 程康文, 李琪, 詹勇強, 等. 5-氟尿嘧啶對肝癌細胞株PLC/RAF/5生物學特性及耐藥機制的影響. 臨床肝膽病雜志, 2015, 31(9):1458-1463.
5. Beulens JW, Booth SL, van den Heuvel EG, et al. The role of mena-quinones (vitamin K2) in human health. Br J Nutr, 2013, 110(8):1357-1368.
6. Hitomi M, Yokoyama F, Kita Y, et al. Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo. Int J Oncol, 2005, 26(3):713-720.
7. Yamamoto T, Nakamura H, Liu W, et al. Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K2. J Gastroenterol, 2009, 44(3):228-235.
8. Zhong JH, Ke Y, Gong WF, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg, 2014, 260(2):329-340.
9. Intaraprasong P, Siramolpiwat S, Vilaichone RK. Advances in management of hepatocellular carcinoma. Asian Pac J Cancer Prev, 2016, 17(8):3697-3703.
10. Hirokawa F, Hayashi M, Miyamoto Y, et al. Outcomes and predic-tors of microvascular invasion of solitary hepatocellular carcinoma. Hepatol Res, 2014, 44(8):846-853.
11. Zhong JH, Ma L, Li LQ. Postoperative therapy options for hepato-cellular carcinoma. Scand J Gastroenterol, 2014, 49(6):649-661.
12. European Association for Study of Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. Eur J Cancer, 2012, 48(5):599-641.
13. Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma for Asia. J Clin Oncol, 2013, 31(28):3501-3508.
14. Kaseb AO, Shindoh J, Patt YZ, et al. Modified cisplatin/inter-feronα-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma. Cancer, 2013, 119(18):3334-3342.
15. 代景友, 楊樹萌, 張新晨, 等. 抑制自噬對5-氟尿嘧啶治療肝癌療效的影響及機制研究. 中國普外基礎與臨床雜志, 2013, 20(8):872-877.
16. Wu J, Hu D, Zhang R. Depletion of Bmi-1 enhances 5-fluorouracil-induced apoptosis and autophagy in hepatocellular carcinoma cells. Oncol Lett, 2012, 4(4):723-726.
17. Zhang H, Ozaki I, Hamajima H, et al. Vitamin K2 augments 5-fluo-rouracil-induced growth inhibition of human hepatocellular carci-noma cells by inhibiting NF-κB activation. Oncol Rep, 2011, 25(1):159-166.
18. Otsuka M, Kato N, Shao RX, et al. Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Hepatology, 2004, 40(1):243-251.
19. Azuma K, Urano T, Ouchi Y, et al. Vitamin K2 suppresses prolifera-tion and motility of hepatocellular carcinoma cells by activating steroid and xenobiotic receptor. Endocr J, 2009, 56(7):843-849.
20. Xia J, Matsuhashi S, Hamajima H, et al. The role of PKC isoforms in the inhibition of NF-κB activation by vitamin K2 in human hepato-cellular carcinoma cells. J Nutr Biochem, 2012, 23(12):1668-1675.
21. Li L, Qi Z, Qian J, et al. Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway. Mol Cell Biochem, 2010, 342(1-2):125-131.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Vitamin K2 Plus 5-Fluorouracil on Proliferation,Migration,and Invasiveness of Hepatocellular Carcinoma Cells

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