Abstract
This study aimed to explore whether the downregulation of LIM kinase 1 (LIMK1)-actin depolymerization factor (ADF, also known as destrin)/cofilin by diallyl disulfide (DADS) inhibited the migration and invasion of colon cancer. Previous studies have shown that silencing LIMK1 could significantly enhance the inhibitory effect of DADS on colon cancer cell migration and invasion, suggesting that LIMK1 was a target molecule of DADS, which needed further confirmation. This study reported that LIMK1 and destrin were highly expressed in colon cancer and associated with poor prognosis of patients with colon cancer. Also, the expression of LIMK1 was positively correlated with the expression of destrin. The overexpression of LIMK1 significantly promoted colon cancer cell migration and invasion. DADS obviously inhibited migration and invasion by suppressing the phosphorylation of ADF/cofilin via downregulation of LIMK1 in colon cancer cells. Furthermore, DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1 in vitro and in vivo, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicated that LIMK1 was a potential target molecule for the inhibitory effect of DADS on colon cancer cell migration and invasion.
Highlights
Colon cancer is one of the most common malignant tumors in humans
The present study confirmed that LIM kinase 1 (LIMK1) and destrin (ADF) were overexpressed in primary colon cancer, which was correlated with the pathological grade, tumor size, clinical stage, lymph node metastasis, and poor prognosis of colon cancer
The expression of LIMK1 protein was positively correlated with the expression of destrin, Figure 5
Summary
Colon cancer is one of the most common malignant tumors in humans. It is the third largest cause of cancer death, and its incidence and mortality rates have increased year after year[1]. LIMK1 activation can promote the phosphorylation of ADF/cofilin (downstream signaling molecules of LIMK1), result in reducing the depolymerization of ADF/cofilin and regulating actin cytoskeletal reorganization, which further promote tumor cell filopodia formation and metastasis[9]. DADS was shown to inhibit colon cancer cell proliferation, migration, and invasion owing to the negative regulation of LIMK1–ADF/cofilin signaling pathway. DADS inhibited the phosphorylation of ADF/cofilin by downregulating the expression of LIMK1, thereby inhibiting colon cancer migration and invasion. These findings suggested that DADS had a significant anticancer effect, indicating that LIMK1 is a potential target molecule for the inhibitory effect of DADS on tumor cell migration and invasion
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