Meiling Yu

Cisplatin (CDDP) is one of the standard first-line chemotherapeutic agents for advanced non-small cell lung cancer (NSCLC). Unfortunately, prolonged exposure to CDDP results in acquired resistance which prevents the successful treatment of lung cancer patients. Thus, it is necessary to explore the mechanism underlying the resistance of NSCLC to CDDP. In the present study, a CDDP-resistant human lung cancer cell line A549/CDDP was established from the parental cell line A549. The results demonstrated that A549/CDDP cells acquired an epithelial-mesenchymal transition (EMT) phenotype, with morphological changes including acquisition of a spindle-like fibroblastic phenotype, downregulation of E-cadherin, upregulation of mesenchymal markers (vimentin, Snail and Slug), and increased capability of invasion and migration. Compared with A549 cells, the A549/CDDP cells showed decreased connexin43 (Cx43) expression. Overexpression of Cx43 reversed EMT and CDDP resistance in the A549/CDDP cells. Conversely, knockdown of Cx43 expression by siRNA-Cx43 initiated EMT and induced CDDP insensitivity in A549 cells. In summary, Cx43 reverses CDDP resistance in A549 CDDP-resistant cells by preventing EMT, making Cx43 a possible therapeutic target for lung cancer.

Previous studies have shown that irinotecan (CPT‑11) impairs chemotherapy‑induced apoptosis by activating nuclear factor‑κB (NF‑κB) and a number of strategies have been employed to augment chemosensitivity through the suppression of NF‑κB activation. Berberine, a botanical alkaloid, was reported to enhance chemosensitivity to 5‑fluorouracil and doxorubicin by suppressing NF‑κB activation. In the present study, the effect of berberine on CPT‑11‑induced apoptosis was investigated through the inhibition of NF‑κB. Inhibition of NF‑κB activation by p65 small interfering RNA was shown to potentiate apoptosis induced by CPT‑11. Berberine suppressed CPT‑11‑induced NF‑κB activation in a dose‑dependent manner and enhanced chemosensitivity to CPT‑11 by downregulating NF‑κB activation of antiapoptotic genes, c‑IAP1, c‑IAP2, survivin and Bcl‑xL. The current observations indicate that berberine inhibits NF‑κB activation and may be used to enhance CPT‑11‑induced apoptosis in colon cancer.

Ginseng has become one of the most commonly used alternative herbal medicines, and its active component, ginsenoside Rg1 has known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have yet to be investigated. In this study, we demonstrated the ability of ginsenoside Rg1 to suppress phorbol myristate acetate (PMA)-induced invasion and migration in MCF-7 breast cancer cells. MCF-7 cells were treated with ginsenoside Rg1 and incubated with or without PMA. The protein and mRNA expression of MMP-9 and MMP-2 was analyzed using Transwell and wound‑healing assays and western blotting. The results showed that suppression was associated with the reduced secretion of MMP-9, a key metastatic enzyme. MMP-9 levels were regulated transcriptionally and correlated with the suppression of NF-κB phosphorylation and DNA binding activity. Conversely, ginsenoside Rg1 did not affect MMP-2 mRNA and TIMP-1 mRNA levels, or the activation of AP-1, suggesting a specificity of pathway inhibition. Inhibition of NF‑κB activation by p65 small‑interfering RNA (siRNA) was shown to suppress PMA-induced cell invasion and migration. The siRNA studies also showed that PMA-induced MMP-9 expression is NF-κB-dependent. The results suggested that the anticancer properties of ginsenoside Rg1 may derive from its ability to inhibit invasion and migration, and that these processes are regulated in breast cancer cells through the NF-κB‑mediated regulation of MMP-9 expression.