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Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma

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Tumor Biology

Abstract

Quercetin (Q), a flavonoid compound, which is obtained in variety of fruits, seeds, and vegetables, has been reported to possess many pharmacological properties including cancer-preventive and anticancer effects. However, studies on the anticancer effects and underlying mechanisms of Q in human hepatocellular carcinoma (HCC) are still limited. The present study is conducted to investigate the anticancer efficacy and adjuvant chemotherapy action of Q in HCC. HCC cell lines HepG2 and SMCC-7721 were treated with different concentrations of Q. The antiproliferative effects of Q were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the apoptosis and cell cycle dynamics were assessed by flow cytometry; the expression of apoptosis-associated proteins were evaluated by Western blot and immunohistochemistry staining; the tumor growth in vivo was evaluated in a xenograft mouse model. Our results showed that Q effectively inhibited human HCC cell proliferation and induced apoptosis by upregulating the expression of Bad and Bax and downregulating the expression of Bcl-2 and Survivin in vitro. Furthermore, Q obviously inhibited the tumor growth and enhanced the 5-fluorouracil (5-FU) therapeutic efficacy in vitro and in vivo. Taken together, our findings highlight that Q effectively inhibited the growth of tumor and enhanced the sensitivity to thermotherapy, indicating Q is a potential treatment option for HCC.

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    Authors and Affiliations

    1. Department of General Surgery, Wujiang No.1 People’s Hospital, Suzhou, 215200, China

      Wei Dai, Quangen Gao, Jianping Qiu, Jianmao Yuan, Guoliang Wu & Genhai Shen

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    1. Wei Dai
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    2. Quangen Gao
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    3. Jianping Qiu
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    4. Jianmao Yuan
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    5. Guoliang Wu
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    6. Genhai Shen
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    Correspondence to Genhai Shen.

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    Ethical approval

    Patient material was obtained with the approval of the ethical committee of the Soochow University and patient agreement. All mouse experiments were approved by the Committee of Care and Use of Laboratory Animals of Yonsei University College of Medicine and performed in accordance with institutional guidelines and policies. The mouse experiments were approved by the Committee of Care and Use of Laboratory Animals of Soochow University of Medicine and performed in accordance with institutional guidelines and policies.

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    Wei Dai and Quangen Gao contributed equally to this work.

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    Fig. S1

    Quercetin increases the expression of Bad and Bax and decrease Bcl-2 and Survivin expression in hepatic cancer cells. HepG2 and SMCC-7721 cells were treated as described above, and the expression of Bad, Bax, Bcl-2 and Survivin were analyzed by western blot. β-Actin served as a control. The relative gray-values (CO = 100 % or Q 0.15 mM group = 100 %) of corresponding bands were calculated and showed in diagrams. The data are presented as means ± SD (**P < 0.01, *P < 0.05). (GIF 39 kb)

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    Dai, W., Gao, Q., Qiu, J. et al. Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma. Tumor Biol. 37, 6307–6313 (2016). https://doi.org/10.1007/s13277-015-4501-0

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    • DOI: https://doi.org/10.1007/s13277-015-4501-0

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