DOWNREGULATION OF KINESIN SPINDLE PROTEIN INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND INCREASES CHEMOSENSITIVITY IN HEPATOCELLULAR CARCINOMA CELLS

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DOAN CHINH CHUNG; DOAN NGOC TRUNG; NGUYEN QUANG HUY; NGUYEN MINH HOA; DO MINH SI; LE VAN DONG

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Journal Paper

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Journal: Iranian Biomedical Journal Year:2015 | Volume:19 | Issue:1 Page(s): 1-16

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Title

DOWNREGULATION OF KINESIN SPINDLE PROTEIN INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND INCREASES CHEMOSENSITIVITY IN HEPATOCELLULAR CARCINOMA CELLS

Author(s)

Keywords

APOPTOSIS

CHEMOSENSITIVITY

DOXORUBICIN

HEPATOCELLULAR CARCINOMA (HCC) CELLS

KINESIN SPINDLE PROTEIN (KSP)

Abstract

Background: Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity.Methods: Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (Cont-siRNA) were transfected into cells. Subsequently, KSP mRNA and protein levels, cell proliferation, and APOPTOSIS were examined in both Hep3B cells and THLE-3 cells. In addition, the CHEMOSENSITIVITY of KSP-siRNA-treated Hep3B cells with DOXORUBICIN was also investigated using cell proliferation and clonogenic survival assays.Results: The expression of endogenous KSP at both mRNA and protein levels in Hep3B cells was higher than in THLE-3 cells. In Hep3B cells, KSP-siRNA #2 showed a further downregulation of KSP as compared to KSP-siRNA #1 or KSP-siRNA #3. It also exhibited greater suppression of cell proliferation and induction of APOPTOSIS than KSP-siRNA #1 or KSP-siRNA #3; this could be explained by the significant downregulation of cyclin D1, Bcl-2, and survivin. In contrast, KSP-siRNAs had no or lower effects on KSP expression, cell proliferation and APOPTOSIS in THLE-3 cells. We also noticed that KSP-siRNA transfection could increase CHEMOSENSITIVITY to DOXORUBICIN in Hep3B cells, even at low doses compared to control.Conclusion: Reducing the expression level of KSP, combined with drug treatment, yields promising results for eradicating hepatocellular carcinoma (HCC) cellsin vitro. This study opens a new direction for liver cancer treatment.

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APA: Copy

DOAN, CHINH CHUNG, DOAN, NGOC TRUNG, NGUYEN, QUANG HUY, NGUYEN, MINH HOA, DO, MINH SI, & LE, VAN DONG. (2015). DOWNREGULATION OF KINESIN SPINDLE PROTEIN INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND INCREASES CHEMOSENSITIVITY IN HEPATOCELLULAR CARCINOMA CELLS. IRANIAN BIOMEDICAL JOURNAL, 19(1), 1-16. SID. https://sid.ir/paper/277389/en

Vancouver: Copy

DOAN CHINH CHUNG, DOAN NGOC TRUNG, NGUYEN QUANG HUY, NGUYEN MINH HOA, DO MINH SI, LE VAN DONG. DOWNREGULATION OF KINESIN SPINDLE PROTEIN INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND INCREASES CHEMOSENSITIVITY IN HEPATOCELLULAR CARCINOMA CELLS. IRANIAN BIOMEDICAL JOURNAL[Internet]. 2015;19(1):1-16. Available from: https://sid.ir/paper/277389/en

IEEE: Copy

CHINH CHUNG DOAN, NGOC TRUNG DOAN, QUANG HUY NGUYEN, MINH HOA NGUYEN, MINH SI DO, and VAN DONG LE, “DOWNREGULATION OF KINESIN SPINDLE PROTEIN INHIBITS PROLIFERATION, INDUCES APOPTOSIS AND INCREASES CHEMOSENSITIVITY IN HEPATOCELLULAR CARCINOMA CELLS,” IRANIAN BIOMEDICAL JOURNAL, vol. 19, no. 1, pp. 1–16, 2015, [Online]. Available: https://sid.ir/paper/277389/en

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