Effects of Combination Treatment with L-Carnitine and 5-Fluorouracil on Proliferation and Apoptosis in MGC803 Cells
LANG Juan-juan1,2, QIAN Xing-yun1, TAO Ruo-lin1, LIU Yan-xia2, WANG Chen1*
1. Department of Pharmacy,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer, Key Laboratory of Tianjin Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer, Tianjin 30060,China; 2. Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China
Abstract��OBJECTIVE To investigate the effects of combination treatment with L-carnitine and 5-fluorouracil on the proliferation and cell apoptosis of gastric cancer MGC803 cells. METHODS MGC803 cells were divided into control group, 5-fluorouracil group and the combination of L-carnitine and 5-fluorouracil group (L-carnitine+/��5-fluorouracil group) in vitro. The inhibitory rate of cells was measured by MTT assay. The apoptosis rate and cell cycle of cells were detected by FLOW. Western blot was used to analyzed the expression of Bcl-2, Bax, adenine nucleotide translocator1(ANT1) and cleaved-PARP. RESULTS Compared with 5-fluorouracil group, the inhibition rate of MGC803 cells was increased when cells were treated with the combination of L-carnitine and 5-fluorouracil. The apoptosis rate of cells was raised and the cells were blocked at S phase. In addition, the combination group can decrease the expression of Bcl-2 and increase the expression of Bax, ANT1 and cleaved-PARP. At the same time, the apoptosis rate of cells and the cell cycle were different with the different dosage regimen when treated with the combination. Compared with the L-carnitine+5-fluorouracil group, the apoptosis rate of cells was increased to (24.17��3.12)% from (19.60��1.06)% (P<0.05). The G0/G1 phase proportion of cells was decreased to (62.62��1.04)% from (72.95��0.91)%,and the S phase proportion of cells was increased to (37.35��1.03)% from (27.05��0.91)% (P<0.001). CONCLUSION Treatment with L-carnitine and 5-fluorouracil could enhance the inhibitory effect of 5-fluorouracil on MGC803 cells. The possible mechanism of action is achieved by regulating the expression of Bcl-2 protein family and influencing the cell cycle.
�ɾ��, Ǯ����, ������, ����ϼ, ����. ����͡���Ϸ�����श�MGC803ϸ����ֳ������Ӱ����о�[J]. �й�ҩѧ��־, 2016, 51(24): 2102-2108.
LANG Juan-juan, QIAN Xing-yun, TAO Ruo-lin, LIU Yan-xia, WANG Chen. Effects of Combination Treatment with L-Carnitine and 5-Fluorouracil on Proliferation and Apoptosis in MGC803 Cells. Chinese Pharmaceutical Journal, 2016, 51(24): 2102-2108.
DENG J, LEI W, XIANG X J, et al. Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway[J]. Oncotarget, 2016, 7(9):10037-10050.
[2]
ZOU W B, LI Z S. Chinese gastric cancer incidence and mortality study progress[J]. Chin J Pract Int Med(�й�ʵ���ڿ���־), 2014,34(4):408-415.
[3]
MATSUSAKA S, LENZ H J. Pharmacogenomics of fluorouracil-based chemotherapy toxicity[J]. Expert Opin Drug Metab Toxicol, 2015, 11(5):811-821.
[4]
WOUTERS K A, KREMER L C, MILLER T L, et al. Protecting against anthracycline-induced myocardial damage:a review of the most promising strategies[J]. Br J Haematol, 2005, 131(5):561-578.
[5]
MINOTTI G, MENNA P, SALVATORELLI E, et al. Anthracyclines:molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity[J]. Pharmacol Rev, 2004, 56(2):185-229.
[6]
SEYMOUR L, BRAMWELL V, MORAN L A. Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group[J]. Cancer Prev Control, 1999, 3(2):145-159.
[7]
EL-ASHMAWY N E, KHALIL R M. A review on the role of carnitine in the management of tamoxifen side effects in treated women with breast cancer[J]. Tumour Biol, 2014, 35(4):2845-2855.
[8]
ALSHABANAH O A, HAFEZ M M, AL-HARBI M M, et al. Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation[J]. Oxid Med Cell Longev, 2010, 3(6):428-433.
[9]
YE Y, WANG C, WANG D, et al. Effect of combination treatment with L-carnitine and epirubicin on proliferation and apoptosis in GLC-82 cell and its mechanism[J]. Chin J Cancer Prev Treat(�л�����������־), 2013, 20(10):744-748.
[10]
SRINIVAS U S, DYCZKOWSKI J, BEISSBARTH T, et al. 5-Fluorouracil sensitizes colorectal tumor cells towards double stranded DNA breaks by interfering with homologous recombination repair[J]. Oncotarget, 2015, 6(14):12574-12586.
[11]
CASALS N, ZAMMIT V, HERRERO L, et al. Carnitine palmitoyltransferase 1C:from cognition to cancer[J]. Prog Lipid Res, 2016, 61(1):134-148.
[12]
RIBAS G S, VARGAS C R, WAJNER M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders[J]. Gene, 2014, 533(2):469-476.
[13]
JIN Y Z, WANG G F, WANG Q, et al. Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats[J]. Mol Biol Rep, 2014, 41(12):7923-7928.
[14]
BI L, YAN X, CHEN W, et al. Antihepatocellular carcinoma potential of tetramethylpyrazine induces cell cycle modulation and mitochondrial-dependent apoptosis:regulation of p53 signaling pathway in HepG2 cells in vitro [J]. Integr Cancer Ther, 2016, 15(2):226-236.
[15]
SONG R S, XIAO X H, LIU Z L, et al. Effects of a monomer purified from paris polyphylla(PP-22) on proliferation and apoptosis of human gastric carcinoma MGC803 cells[J]. Chin Pharm J(�й�ҩѧ��־), 2015, 50(18):1600-1606.
[16]
BAINES C P, MOLKENTIN J D. Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax[J]. J Mol Cell Cardiol, 2009, 46(6):969-977.
[17]
JANG J Y, CHOI Y, JEON Y K, et al. Over-expression of adenine nucleotide translocase 1 (ANT1) induces apoptosis and tumor regression in vivo[J]. BMC Cancer, 2008, 8(4):160-169.
[18]
RUGGIERI S, ORSOMANDO G, SORCI L, et al. Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues[J]. Biochim Biophys Acta, 2015, 1854(9):1138-1149.
[19]
ZOVKO A, VIKTORSSON K, HAAG P, et al. Marine sponge Cribrochalina vasculum compounds activate intrinsic apoptotic signaling and inhibit growth factor signaling cascades in non-small cell lung carcinoma[J]. Mol Cancer Ther, 2014, 13(12):2941-2954.
[20]
XAVIER PINTO M C, KIHARA A H, GOULART V A M, et al. Calcium signaling and cell proliferation[J]. Cell Signal, 2015, 27(11):2139-2149.
2016, Vol. 51 
