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Article

Research article

J. Microbiol. Biotechnol. 2016; 26(8): 1490-1503

Published online August 28, 2016 https://doi.org/10.4014/jmb.1605.05024

Copyright © The Korean Society for Microbiology and Biotechnology.

Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells

JaeJin An 1 and Eun-Mi Ha 2*

1Medical Convergence Textile Center, Gyeongbuk Technopark, Gyeongsangbuk-do 38412, Republic of Korea, 1Department of Pharmacology, College of Pharmacy, Catholic University of Daegu 38430, Republic of Korea

Received: May 10, 2016; Accepted: May 23, 2016

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-
fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has
therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop
into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors.
The human gastrointestinal tract contains a complex gut microbiota that is essential for the
host’s homeostasis. Recently, many studies have reported correlations between gut flora and
the onset, progression, and treatment of CRC. The present study confirms that the most
representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN),
selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT-
116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of
CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to
cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced
an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC
cells, and reducing the formation and size of colonospheres. In conclusion, our results show
that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal
cancer stem-like cells by reversing the development of resistance to anticancer drugs. This
implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for
chemoresistant CRC.

Keywords: Lactobacillus plantarum, 5-Fluorouracil, colorectal cancer cells, chemoresistant, cancer stem cells

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