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 daripada 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

Diserahkan: 28 Jun 2014/Diterima: 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

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