Study summary · research use only
Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study combining in vitro human hepatocellular carcinoma (HCC) cell experiments and in vivo mouse xenograft models, researchers examined the effects of Cathelicidin hCAP18/LL-37 on HCC. The abstract reports hCAP18/LL-37 overexpression significantly promoted proliferation of cultured HCC cells and growth of PLC/PRF-5 xenograft tumors in mice. Transcriptome sequencing identified the PI3K/Akt pathway as most significantly upregulated with LL-37 overexpression, and hCAP18/LL-37 stimulated phosphorylation of EGFR/HER2 and activated PI3K/Akt signaling in HCC cells, with stronger EGFR/HER2/Akt signals also seen in xenograft tumors. Although hCAP18/LL-37 was downregulated in HCC cells and tumors, 1,25(OH)2D3 treatment upregulated hCAP18/LL-37 levels in both, and 1,25(OH)2D3 combined with si-LL-37 was associated with greater reduction of xenograft tumor growth than 1,25(OH)2D3 alone.
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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