2. Academic Validation
  3. Triptolide enhances chemotherapeutic efficacy of antitumor drugs in non-small-cell lung cancer cells by inhibiting Nrf2-ARE activity

Triptolide enhances chemotherapeutic efficacy of antitumor drugs in non-small-cell lung cancer cells by inhibiting Nrf2-ARE activity

  • Toxicol Appl Pharmacol. 2018 Nov 1;358:1-9. doi: 10.1016/j.taap.2018.09.004.
Jiayu Zhu 1,  Huihui Wang 2,  Feng Chen 3,  Hang Lv 1,  Zijin Xu 1,  Jingqi Fu 1,  Yongyong Hou 1,  Yuanyuan Xu 1,  Jingbo Pi 4
Affiliations

Affiliations

  • 1 Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New area, Shenyang 110122, China.
  • 2 Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New area, Shenyang 110122, China. Electronic address: hhwang@cmu.edu.cn.
  • 3 Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Road, Heping Area, Shenyang, 110001, China; Interventional Department, Qianfoshan Hospital, Shandong University, No.16766 Jingshi Road, Jinan 250014, China.
  • 4 Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New area, Shenyang 110122, China. Electronic address: jbpi@cmu.edu.cn.
PMID: 30196066 DOI: 10.1016/j.taap.2018.09.004
Abstract

Non-small cell lung Cancer (NSCLC) has a high mortality rate worldwide. Various treatments strategies have been used against NSCLC including individualized chemotherapies, but innate or acquired Cancer cell drug resistance remains a major obstacle. Recent studies revealed that the Kelch-like ECH associated protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway is intimately involved in Cancer progression and chemoresistance. Thus, antagonizing Nrf2 would seem to be a viable strategy in Cancer therapy. In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various Cancer cells, including NSCLC and liver Cancer cells. Consequently, triptolide made Cancer cells more chemosensitivity toward antitumor drugs both in vitro and in a xenograft tumor model system using lung carcinoma cells. These results suggest that triptolide blocks chemoresistance in Cancer cells by targeting the Nrf2 pathway. Triptolide should be further investigated in clinical Cancer trials.

Keywords

Chemoresistance; NSCLC; Nrf2; Triptolide.

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