1. Academic Validation
  2. Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)2D3 in hepatocellular carcinoma

Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)2D3 in hepatocellular carcinoma

  • Cell Death Discov. 2022 Jan 17;8(1):27. doi: 10.1038/s41420-022-00816-w.
Huidan Zhang 1 Junai Zhen 1 Rong Zhang 1 Yangke Wanyan 1 Kehang Liu 1 Xueli Yuan 1 Liping Tao 1 Yuqing Chen 2
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing, China.
  • 2 Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing, China. yuqingchen515@yahoo.com.
Abstract

Cathelicidin hCAP18/LL-37 can resist Infection from various pathogens and is an essential component of the human immune system. Accumulating evidence has indicated that hCAP18/LL-37 plays a tissue-specific role in human Cancer. However, its function in hepatocellular carcinoma (HCC) is poorly understood. The present study investigated the effects of hCAP18/LL-37 on HCC in vitro and in vivo. Results showed that hCAP18/LL-37 overexpression significantly promoted the proliferation of cultured HCC cells and the growth of PLC/PRF-5 xenograft tumor. Transcriptome Sequencing analyses revealed that the PI3K/Akt pathway was the most significant upregulated pathway induced by LL-37 overexpression. Further analysis demonstrated that hCAP18/LL-37 stimulated the phosphorylation of EGFR/HER2 and activated the PI3K/Akt pathway in HCC cells. Furthermore, stronger EGFR/HER2/Akt signals were observed in the PLC/PRF-5LL-37 xenograft tumor. Interestingly, even though the expression of hCAP18/LL-37 was significantly downregulated in HCC cells and tumors, 1,25(OH)2D3 treatment significantly upregulated the hCAP18/LL-37 level both in HCC cells and xenograft tumors. Moreover, 1,25(OH)2D3 together with si-LL-37 significantly enhanced the antitumor activity of 1,25(OH)2D3 in the PLC/PRF-5 xenograft tumor. Collectively, these data suggest that hCAP18/LL-37 promotes HCC cells proliferation through stimulation of the EGFR/HER2/Akt signals and appears to suppress the antitumor activity of 1,25(OH)2D3 in HCC xenograft tumor. This implies that hCAP18/LL-37 may be an important target when aiming to improve the antitumor activity of 1,25(OH)2D3 supplementation therapy in HCC.

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