Sulforaphane reverses gefitinib tolerance in human lung cancer cells via modulation of sonic hedgehog signaling

Wang,Fanping; Wang,Wenjun; Li,Junpeng; Zhang,Jingjing; Wang,Xia; Wang,Mingyong

doi:10.3892/ol.2017.7293

Sulforaphane reverses gefitinib tolerance in human lung cancer cells via modulation of sonic hedgehog signaling

Authors:
- Fanping Wang
- Wenjun Wang
- Junpeng Li
- Jingjing Zhang
- Xia Wang
- Mingyong Wang
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Affiliations: School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Cancer Research Institute, Sun Yat‑sen Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: October 30, 2017 https://doi.org/10.3892/ol.2017.7293
Pages: 109-114
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gefitinib is a targeted anticancer drug that was developed as an effective clinical therapy for lung cancer. Numerous patients develop gefitinib resistance in response to treatment. Sulforaphane (SFN) is present in cruciferous vegetables, and has been demonstrated to inhibit the malignant growth of various types of cancer cells. To investigate the role of SFN in gefitinib resistance, a gefitinib‑tolerant PC9 (PC9GT) cell model was established by continually exposing PC9 cells to gefitinib. Cell viability was measured using a cell proliferation assay. Components of the sonic hedgehog (SHH) signaling pathway and markers of lung cancer stem cells were detected via western blotting. SFN markedly inhibited the proliferation of PC9GT and PC9 cells in a dose‑dependent manner; combination SFN/gefitinib treatment also markedly decreased PC9GT cell proliferation, compared with SFN or gefitinib administered alone (P<0.05). Western blot analysis revealed that the expression of SHH, Smoothened (SMO), zinc finger protein GLI1 (GLI1), GLI2, CD133 and CD44 were upregulated in PC9GT cells, as compared with in PC9 cells. Furthermore, SFN markedly inhibited the expression of SHH, SMO and GLI1 in PC9GT and PC9 cells in a dose dependent manner, and SFN combined with gefitinib markedly inhibited the expression of SHH, SMO, GLI1, CD133 and CD44 in PC9GT cells when compared with SFN or gefitinib monotherapy. The results of the present study demonstrated that SFN inhibits the proliferation of gefitinib‑tolerant lung cancer cells via modulation of the SHH signaling pathway. Therefore, combined SFN and gefitinib therapy may be an effective approach for the treatment of lung cancer.

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