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Sains Malaysiana 45(1)(2016):
109–113 Matrine Enhances the Inhibitory Effect
of 5-FU on SW480 Cells
in vitro and in vivo (Matrin Meningkatkan Kesan Perencatan 5-FU pada Sel SW480
in vitro dan in vivo) XU-HUI
ZHANG2*,
LEI
LIANG1,
XIAO-YAN
WANG3,
LI
ZHANG4,
YAN-XIN
ZHENG4,
HONG-ZHU
DENG4
& XIN-RONG WU1
1Department of Pharmacy,
Guangzhou General Hospital of Guangzhou Military Command Guangzhou, 510010,
China 2Department of Oncology,
Guangdong No. 2 Provincial People’s Hospital, Guangzhou, 510317,
China 3School of Basic
Medical Sciences, Southern Medical University, Guangzhou 510515,
China 4School of Traditional
Chinese Medicine, Southern Medical University, Guangzhou 510515 China Received: 28 June
2014/Accepted: 10 November 2014 ABSTRACT
We investigated the antitumor
effects of the combination of matrine-a purified alkaloid extracted
from Sophora flavescence-and 5-fluorouracil
(5-FU) on SW480
cells. This combination inhibited the growth of SW480
cells in a synergistic or additive manner by disrupting their progression
through the cell cycle. Exposure of SW480 cells to matrine and 5-FU
was followed by an increased rate of expression for
caspase-3, caspase-9 and poly-ADP
ribose polymerase (PARP) and inhibited the subcutaneous transplantation of
SW480
tumors into Balb/c nude mice. Histopathological analysis showed
that this effect was most pronounced in the spleens of treated animals.
Typical cytotoxic effects observed in 5-FU-treated mice included fibrosis and
lymphopenia, whereas in mice treated with 5-FU combined
with matrine, the spleen ultrastructure remained intact. These findings
indicate that matrine may enhance the therapeutic effectiveness
of 5-FU
in SW480
tumors by enhancing apoptosis and overcome the threat to immunocompetence
associated with 5-FU. Keywords: Colorectal cancer;
combination chemotherapy; cytotoxicity; Sophora
flavescence; 5-fluorouracil ABSTRAK
Kami mengkaji kesan antitumor
daripada gabungan matrin - alkaloid yang ditulenkan diekstrak daripada
Sophora flavescence dan 5-fluorourasil
(5-FU) pada sel SW480.
Gabungan ini menghalang pertumbuhan sel SW480 secara sinergi atau tambahan
dengan mengganggu perkembangan mereka melalui kitaran sel. Pendedahan
sel SW480 kepada matrine dan 5-FU diikuti
dengan kadar peningkatan ekspresi untuk caspase-3, caspase-9 dan
poli-ADP
ribosa polimerase (PARP) dan menghalang pemindahan subkutaneus tumor SW480
ke tikus bogel Balb/c. Analisis histopatologi menunjukkan bahawa
ini memberi kesan paling ketara dalam limpa haiwan yang dirawat.
Kesan sitotoksik biasa diperhatikan dalam tikus 5-FU-dirawat termasuk fibrosis dan limfofenia,
manakala pada tikus yang dirawat dengan 5-FU digabungkan
dengan matrin, ultrastruktur limpa kekal utuh. Penemuan ini menunjukkan
bahawa matrin boleh meningkatkan keberkesanan terapeutik 5-FU dalam
tumor SW480 dengan meningkatkan apoptosis dan mengatasi ancaman
kepada kecekapanimuno yang dikaitkan dengan 5-FU.
Kata kunci: Gabungan kemoterapi; kanser kolorektal; sitotoksiti;
Sophora flavescence; 5-fluorourasil REFERENCES
Broker, L.E., Kruyt,
F.A.E. & Giaccone, G. 2005. Cell death independent of caspases:
A review. Clinical Cancer Research 11(9): 3155-3162. Chen, J., Mei,
Q., Xu, Y.C., Du, J., Wei, Y. & Xu, Z.M. 2006. Effects of matrine
injection on T-lymphocyte subsets of patients with malignant tumor
after gamma knife radiosurgery. Zhong Xi Yi Jie He Xue Bao 4(1):
78-79. Crew, K.D. &
Neugut, A.I. 2006. Epidemiology of gastric cancer. World Journal
of Gastroenterology 12(3): 354-362. Dai, Z.J., Gao,
J., Ji, Z.Z., Wang, X.J., Ren, H.T., Liu, X.X., Wu, W.Y., Kang,
H.F. & Guan, H.T. 2009. Matrine induces apoptosis in gastric
carcinoma cells via alteration of Fas/FasL and activation
of caspase-3. Journal of Ethnopharmacology 23(1): 91-96.
Dai, Z.J., Wu,
W.Y., Wang, X.J., Xue, X.H., Liu, X.X. & Xue, F.J. 2005. Effect
of Fufangmatrine on immunity of patient with metaphase and late
lung squamous carcinoma treated with chemotherapy. Journal of
Beijing University of Traditional Chinese Medicine 28: 77-79.
Jiang, H., Hou,
C., Zhang, S., Xie, H., Zhou, W., Jin, Q., Cheng, X., Qian, R. &
Zhang, X. 2007. Matrine upregulates the cell cycle protein E2F-1
and triggers apoptosis via the mitochondrial pathway in K562 cells.
European Journal of Pharmacology 559(2-3): 98-108. Lin, C-H., Wang, Y. & Xiao, R-P. 2011. Effect of cis-platinum
(DDP) combined with matrine on CEA and immune function in malignant
pleural effusion. Hainan Medical Journal 10: 38-40. Liu, X.S., Jiang,
J., Jiao, X.Y., Wu, Y.E. & Lin, J.H. 2006. Matrine-induced apoptosis
in leukemia U937 cells: Involvement of caspases activation and MAPK-independent
pathways. Planta Medica 72(6): 501-506. Lopez-Hernandez,
F.J., Ortiz, M.A., Bayon, Y. & Piedrafita, F.J. 2003. Z-FA-fmk
inhibits effector caspases but not initiator caspases 8 and 10,
and demonstrates that novel anticancer retinoid-related molecules
induce apoptosis via the intrinsic pathway. Molecular Cancer
Therapeutics 2: 255-263. Luo, C., Zhu, Y., Jiang, T., Lu, X., Zhang, W., Jing, Q., Li,
J., Pang, L., Chen, K., Qiu, F., Yu, X., Yang, J. & Huang, J.
2007. Matrine induced gastric cancer MKN45 cells apoptosis via increasing
pro-apoptotic molecules of Bcl-2 family. Toxicology 229(3):
245-252. Han, Y., Zhang,
S., Wu, J., Yu, K., Zhang, Y., Yin, L. & Bi, L. 2010. Matrine
induces apoptosis of human multiple myeloma cells via activation
of the mitochondrial pathway. Leukemia & Lymphoma 51:
1337-1346. Ma, L., Wen, S.,
Zhan, Y., He, Y., Liu, X. & Jiang, J. 2008. Anticancer effects
of the Chinese medicine matrine on murine hepatocellular carcinoma
cells. Planta Medica 74: 245-251. Mizutani, Y., Nakanishi,
H., Li, Y.N., Sato, N., Kawauchi, A. & Miki, T. 2004. Enhanced
sensitivity of bladder cancer cells to cisplatin mediated cytotoxicity
and apoptosis in vitro and in vivo by the selective
cyclooxygenase-2 inhibitor JTE-522. J. Urol. 172(4): 1474-1479.
Yamazaki, M. 2000.
The pharmacological studies on matrine and oxymatrine. Journal
of the Pharmaceutical Society of Japan 120(10): 1025-1033. Yang, C.L., Liu,
S.S., Ma, Y.G., Liu, Y.Y., Xue, Y.X. & Huang, B. 2012. The influence
of intraoperative pleural perfusion with matrine-cisplatin or cisplatin
on stromal cell-derived factor-1 in non-small cell lung cancer patients
with subclinical pleural metastasis. Medical Oncology 29(2):
574-581. Yu, P., Liu, Q.,
Liu, K., Yagasaki, K., Wu, E. & Zhang, G. 2009. Matrine suppresses
breast cancer cell proliferation and invasion via VEGF-Akt-NF-kappaB
signaling. Cytotechnology 59: 219-229. Zhang, J., Li,
Y., Chen, X., Liu, T., Chen, Y., He, W., Zhang, Q. & Liu, S.
2011. Autophagy is involved in anticancer effects of matrine on
SGC-7901 human gastric cancer cells. Oncology Report 26(1):
115-124. Zhang, Y., Wang,
S., Li, Y., Xiao, Z., Hu, Z. & Zhang, J. 2008. Sophocarpine
and matrine inhibit the production of TNF-alpha and IL-6 in murine
macrophages and prevent cachexia-related symptoms induced by colon26
adenocarcinoma in mice. International Immunopharmacology 8:
1767-1772. Zhang, L., Wang,
T., Wen, X., Wei, Y., Peng, X., Li, H. & Wei, L. 2007. Effect
of matrine on HeLa cell adhesion and migration. European Journal
of Pharmacology 563(1-3): 69-76. Zhang, L.P., Jiang,
J.K., Tam, J.W., Zhang, Y., Liu, X.S., Xu, X.R., Liu, B.Z. &
He, Y.J. 2001. Effects of matrine on proliferation and differentiation
in K-562 cells. Leukemia Research 25(9): 793-800. Zhao, L., Wang,
H., Liu, C., Liu, Y., Wang, X., Wang, S., Sun, X., Li, J., Deng,
Y., Jiang, Y. & Ding, Y. 2010. Promotion of colorectal cancer
growth and metastasis by the LIM and SH3 domain protein 1. Gut
59: 1226-1235. Zhu, Z.C., Wang,
H.Z. & Yang, F. 2009. Composite sophorae injection in prevention
of toxicity and adverse effects caused by chemotherapeutic agents.
Journal of Practical Oncology 24(6): 592-594. *Corresponding author; email: bloomtree@hotmail.com
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