SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2

Abstract

The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial. Studies have demonstrated that small integrin-binding ligand N-linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis. SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP-2) and MMP-9 expression. Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells. In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability. A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen-independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen-dependent prostate cancer cells. Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP-2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation. Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP-2 were also inhibited.

Insulin promotes invasion and migration of KRASG12D mutant HPNE cells by upregulating MMP‐2 gelatinolytic activity via ERK‐ and PI3K‐dependent signalling

“…In addition, insulin also increased the phosphorylation of JNK and p38 MAPKs. 70,71 The present study provided information that the insulin-promoted MMP-2 gelatinolytic activity was upregulated partly through PI3K/AKT/mTOR signalling. These results suggested a feedback also observed in other pancreatic cell lines.…”

“…67,68 mTOR is a significant downstream protein of PI3K/AKT pathway, and activation of mTOR by p-AKT can upregulate the expression of MMP-2 in multiple tumours, including pancreatic cancer. 70,71 The present study provided information that the insulin-promoted MMP-2 gelatinolytic activity was upregulated partly through PI3K/AKT/mTOR signalling. Taken together, our findings suggest that insulin-induced activation of ERK1/2 MAPK and PI3K/AKT/mTOR signalling may be involved in the invasion and migration through the upregulation of MMP-2 gelatinolytic activity.…”

The Axin2-snail Axis Promotes Bone Invasion by Activating Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma

“…In the present study, recombinant IL8 can increase the invasion ability of CAFs in vitro. In various type of cancer tissues, IL8 can participate in the degradation of the extracellular matrix by promoting the expression of MMP-2 and MMP-9 in cancer cells [46][47][48][49]. According to public data base analysis, MMP-9 acts in a context-dependent manner in different types of cancers [50].…”

The Axin2-Snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma

“…In the present study, recombinant IL8 increased the invasion ability of CAFs in vitro. In various types of cancer tissues, IL8 participates in degradation of the extracellular matrix by promoting the expression of MMP-2 and MMP-9 in cancer cells [50][51][52][53]. According to an analysis of a public data base, MMP-9 acts in a context-dependent manner in different types of cancer [54].…”