The treatment of cetuximab-resistant colorectal cancer (CRC) remains a major problem. The study was to assess the potential effects of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a type of therapeutic biological product approved in China, on cetuximab-resistant CRC and further explore the underlying mechanism. MiRNA sequencing was used to screen the differential expression profile of miRNAs. Cell proliferation, apoptosis, migration and invasion were detected by cell counting kit-8, flow cytometry, wound healing and transwell assays, respectively. PA-MSHA drastically inhibited the migration and invasion, and induced the apoptosis of cetuximab-resistant CRC cells. PA-MSHA also potently inhibited tumour growth and increased the survival time of mice in vivo. These results indicated that PA-MSHA exerted potent activity against cetuximab-resistant CRC. The sequencing data showed that miR-7-5p was markedly upregulated after PA-MSHA treatment, and miR-7-5p overexpression positively enhanced the anticancer activities of PA-MSHA in vitro and in vivo. Luciferase reporter assay confirmed that Akt was the targeted gene of miR-7-5p, and Akt silencing could reverse the PA-MSHA efficacy inhibited by miR-7-5p downregulation. In addition, PA-MSHA treatment markedly inhibited the activation of Wnt-β-catenin pathway, a downstream signaling of Akt. Moreover, Akt silencing inhibited the Wnt-β-catenin pathway activated by miR-7-5p downregulation in PA-MSHA-treated HCT116-R cells. Finally, we found that serum miR-7-5p levels were significantly lower in CRC patients with cetuximab resistance or disease progression. Overall, our data showed that PA-MSHA exerted potent activity against cetuximab-resistant CRC by regulating miR-7-5p/Akt/Wnt-β-catenin pathway. These results indicate that PA-MSHA may be a novel and effective chemotherapeutic agent against cetuximab-resistant CRC.
Background To find the relationship between prostaglandin E receptor 2 (EP 2 ) and epidermal growth factor receptor (EGFR) in esophageal squamous cell carcinoma (ESCC) patients with regional lymph nodes metastasis (pN+) who had undergone curative resection, and to analyze them in the role of judging prognosis. Methods Sixty-three patients with ESCC who underwent attempted curative esophagectomy with lymph node metastasis were collected. Immunohistochemistry (IHC) was used to analyse the expression of EP 2 and EGFR in tumor tissues. We analyzed the relationship between the two markers. Furthermore, we analyzed the role of EP 2 and EGFR in disease-free survival (DFS) and overall survival (OS). Results The expression rate of EP 2 and EGFR in this study were 73.0%, 85.7%, respectively. And the EP 2 status was closely related with the expression of EGFR in tumor tissues (χ 2 =0.260, P=0.011). The patients with EP 2 or EGFR positive expression had a shorter DFS and OS than the negative group. Further analysis found EGFR is an important prognostic factor for DFS and OS (P<0.001), the expression of EP 2 was related with PFS (P=0.048), but it was not an independent influencing factors for OS (P>0.05). Conclusions The expression of EP 2 and EGFR were high in tumor tissues of (pN+) ESCC, and they are playing a key role in the prognosis of ESCC patients with local lymph node metastases.
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