2. Academic Validation
  3. Suppression of fumarate hydratase activity increases the efficacy of cisplatin-mediated chemotherapy in gastric cancer

Suppression of fumarate hydratase activity increases the efficacy of cisplatin-mediated chemotherapy in gastric cancer

  • Cell Death Dis. 2019 May 28;10(6):413. doi: 10.1038/s41419-019-1652-8.
Hong-En Yu 1,  Feng Wang 1 2,  Fang Yu 3,  Zhao-Lei Zeng 1 2,  Yun Wang 1,  Yun-Xin Lu 1 2,  Ying Jin 1 2,  De-Shen Wang 1 2,  Miao-Zhen Qiu 1 2,  Heng-Ying Pu 1,  Tie-Bang Kang 1,  Dan Xie 1,  Huai-Qiang Ju 4,  Rui-Hua Xu 5 6,  Hui-Yan Luo 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
  • 2 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
  • 3 Department of Health Examination, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510700, P. R. China.
  • 4 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. juhq@sysucc.org.cn.
  • 5 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. xurh@sysucc.org.cn.
  • 6 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China. xurh@sysucc.org.cn.
  • 7 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. luohy@sysucc.org.cn.
  • 8 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China. luohy@sysucc.org.cn.
PMID: 31138787 DOI: 10.1038/s41419-019-1652-8
Abstract

Gastric Cancer (GC) is one of the most common malignancies worldwide. Due to the low rate of early detection, most GC patients were diagnosed as advance stages and had poor response to chemotherapy. Some studies found that Fumarate hydratase (FH) participated in the DNA damage response and its deficiency was associated with tumorigenesis in some cancers. In this study, we investigated the relationship between FH and cisplatin (CDDP) sensitivity in GC cell lines. We found that FH was the most significant gene which induced by CDDP treatment and the suppression of FH could enhance the cytotoxicity of CDDP. Miconazole Nitrate (MN) could inhibit FH activity and enhance the effect of CDDP in vitro and in vivo. We also investigated the significance of expression of FH in GC tissues. The FH expression, which was higher in GC tissues than in noncancerous tissues, was negatively associated with the prognosis of patients. Together, these results revealed that FH is a reliable indicator for response to CDDP treatment in GC and the inhibition of FH may be a potential strategy to improve the effects of CDDP-based chemotherapy.

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