Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway

Zhang,Tianxiang; Zhang,Xi; Fei,Yang; Lu,Jinsen; Zhou,Dairan; Zhang,Li; Fan,Song; Zhou,Jun; Liang,Chaozhao; Su,Yang

doi:10.3892/ijo.2024.5658

Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway

Authors:
- Tianxiang Zhang
- Xi Zhang
- Yang Fei
- Jinsen Lu
- Dairan Zhou
- Li Zhang
- Song Fan
- Jun Zhou
- Chaozhao Liang
- Yang Su
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Affiliations: Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Urology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, State Key Laboratory of Systems Medicine for Cancer, Department of Urology, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China, Nufﬁeld Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK, Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China
Published online on: May 29, 2024 https://doi.org/10.3892/ijo.2024.5658
Article Number: 70
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit‑8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylin‑eosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcription‑quantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786‑O and ACHN) than the effect on normal renal tubular epithelial cell (HK‑2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dose‑dependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.

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