2. Academic Validation
  3. Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin

Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin

  • J Pharm Pharmacol. 2024 Feb 8:rgad116. doi: 10.1093/jpp/rgad116.
Enhui Gong 1,  Jiongwei Pan 1,  Zaiting Ye 2,  Xiaoping Cai 1,  Hao Zheng 1,  Zhangyong Yin 1,  Yiwei Jiang 3,  Xin Wang 3,  Zhuo Cao 1 4
Affiliations

Affiliations

  • 1 Respiratory Department, The Sixth Affiliated Hospital of Wenzhou Medical University, 15# Dazhong Street, Liandu District, Lishui City, Zhejiang Province, China.
  • 2 Radiology Department, The Sixth Affiliated Hospital of Wenzhou Medical University, 15# Dazhong Street, Liandu District, Lishui City, Zhejiang Province, China.
  • 3 Graduate Department, Wenzhou Medical University, Wenzhou, University Town, Chashan, Wenzhou, Zhejiang, P.R China.
  • 4 Respiratory Department, Longquan People's Hospital, No. 699 Dongcha Road, Longquan City, Zhejiang Province, China.
PMID: 38330446 DOI: 10.1093/jpp/rgad116
Abstract

Objectives: Reportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung Cancer cells.

Methods: After the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative Reverse transcription PCR (qRT-PCR). The DDP-resistant lung Cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A.

Results: GA-A suppressed the viability, migration, and invasion while downregulating Beclin and Autophagy marker LC3II/LC3I levels and upregulating p62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the Apoptosis and regulated the circFLNA/miR-486-3p/Cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and Apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung Cancer tumor growth and blocked Autophagy.

Conclusion: GA-A suppresses Autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung Cancer cells to DDP.

Keywords

autophagy; circRNA filamin A; cisplatin resistance; ganoderic acid A; lung cancer.

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