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Differentiation-inducing activity of hydroxycamptothecin on cancer stem-like cells derived from hepatocellular
Yi Zhang1, Wen-Jie Song, Fu-Qin Zhang
1Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changlexi Road, Xi'an, Shaanxi Province, 710032, People's Republic of China.
Background:
Hydroxycamptothecin (HCPT) is an anti-tumor agent that can induce differentiation in human cancer cells. Recent evidence indicates that side population (SP) cells possess characteristics of stem-like cells, and may be capable of initiating tumor growth.
Aims:
The present study investigated the differentiation of cancer stem-like cells derived from hepatocellular carcinoma.
Methods And Results:
Flow cytometry was used to isolated SP cells from HCC cell line (MHCC97 cells). These SP cells exhibit several stem-like cell characteristics that are distinct from the main population (MP) cells in vitro. After 3 days of induction with a low concentration of HCPT, the SP cells lost their capacity to proliferate and invade, and their tumorigenicity declined. Based on real-time quantitative RT-PCR, we also found that the expression of hepatocyte-specific markers such as α-fetoprotein, albumin, hepatocyte nuclear factor-4 and miR-122 gradually changed during the differentiation of SP cells.
Conclusions:
Our data suggest that a low concentration of HCPT can induce hepatocyte-specific differentiation of cancer stem-like cells from MHCC97 cells, offering a possible therapeutic strategy for the treatment of human malignancies.
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