Gambogic acid increases the sensitivity to paclitaxel in drug‑resistant triple‑negative breast cancer via the SHH signaling pathway

Wang,Yonghui; Sui,Yana; Tao,Yinggang

doi:10.3892/mmr.2019.10697

Gambogic acid increases the sensitivity to paclitaxel in drug‑resistant triple‑negative breast cancer via the SHH signaling pathway

Authors:
- Yonghui Wang
- Yana Sui
- Yinggang Tao
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Affiliations: Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Emergency Department of Weifang Traditional Chinese Hospital, Weifang, Shandong 261041, P.R. China, Department of General Surgery, Weifang Second People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: September 23, 2019 https://doi.org/10.3892/mmr.2019.10697
Pages: 4515-4522
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paclitaxel is the most frequently used therapy regimen for triple‑negative breast cancer (TNBC). However, chemoresistance frequently occurs, leading to enhanced failure rates of chemotherapy in TNBC; therefore, novel biological therapies are urgently needed. Gambogic acid (GA) has potent anticancer effects and inhibits tumor growth in several types of human cancer. However, the effects of GA on paclitaxel‑resistant TNBC remain unknown. In the present study, the Cell Counting Kit‑8 assay was used to examine the effect of GA and/or paclitaxel on the viability of TNBC cells; flow cytometry was used to examine the effects of GA on cell apoptosis; and western blotting and reverse transcription‑quantitative PCR were used to determine the effects of GA on the expression of sonic hedgehog (SHH) signaling pathway target genes. The present results indicated that GA significantly inhibited the viability and enhanced the rate of apoptosis in paclitaxel‑resistant MDA‑MB‑231 cells via activating the SHH signaling pathway. In vivo experiments confirmed that GA treatment enhanced the sensitivity of MDA‑MB‑231 cells to paclitaxel via the SHH signaling pathway. In conclusion, the combination of GA with paclitaxel may increase the antitumor effects on paclitaxel‑resistant TNBC via downregulating the SHH signaling pathway.

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