Targeted silencing of CXCL1 by siRNA inhibits tumor growth and apoptosis in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy and a major cause of cancer-related mortality worldwide. Our previous study shows that chemokine (C-X-C motif) ligand 1 (CXCL1) was upregulated and CXCR1 was downregulated in tumor tissues as compared to peritumor tissues by chemotaxis assay. As the status of CXCL subgroups and their receptors affect progression of HCC, we evaluated potential mechanisms of CXCL1 associated with anticancer effects in HCC based on our previous study. The effects of targeting CXCL1 by RNA interference (RNAi) on the proliferation and apoptosis of CBRH-7919 cells were observed in vitro and in vivo. Additionally, whether CXCL1 knockdown significantly reduce the activity of STAT3, NF-κB and HIF-1 or not were also estimated. RNAi of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice by inhibited cells proliferation and induced apoptosis. In conclusion, these findings suggest that CXCL1 plays critical roles in the growth and apoptosis of HCC. RNAi of CXCL1 inhibits the growth and apoptosis of tumor cells, which indicates that CXCL1 may be a potential molecular target for use in HCC therapy.

Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

“…Furthermore, CXCL1-mediated myeloid cells infiltration is associated with therapeutic response in breast cancer [ 17 ]. Recently, it has been reported that stably silencing of CXCL1 can inhibit tumor growth in HCC [ 18 ], and knocking down of CXCL1 expression can inhibit tumor growth in colorectal liver metastasis [ 19 ]. Additionally, autocrine and paracrine of CXCL1 can also promote tumor invasion and metastasis [ 17 , 20 , 21 ].…”

An Autocrine Role for CXCL1 in Progression of Hepatocellular Carcinoma

“…Therapy with respect to CXCL1 and CXCR2 has been explored, however, not in the context of nutritional or metabolic modification. In xenograft models, reduced tumor size was observed either when CXCL1 was knocked down by small interfering RNA in HCC cells (36), or when animals were treated with therapeutic T-cells transduced with CXCR2 (37). In conclusion, we demonstrate here a role for palmitate in the up-regulation of an autocrine signaling axis involving CXCL1 and CXCR2.…”

Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates cisplatin-induced acute kidney injury in mice

“…IL-1β and IL-6 have been shown to be important inflammatory markers upregulated in the kidneys following cisplatin [ 40 ]. Likewise, CXCL1, produced during cisplatin-AKI potentially by T lymphocytes in the kidneys [ 41 ], is a well-known neutrophil chemoattractant capable of inducing apoptosis [ 42 ]. Previous studies report that α7nAChR -/- mice show excessive CXCL1 production and uncontrolled neutrophil infiltration compared to wild-type mice after challenge with immune complexes [ 43 ].…”