chondroitin-sulfates and Carcinoma--Non-Small-Cell-Lung

Non-small cell lung cancer (NSCLC) is a malignant cancer worldwide. Long non-coding RNAs (lncRNAs) have emerged as key players in the development and progression of NSCLC, and may be potential biomarkers of NSCLC. Here, we investigated the clinical significance of lncRNA oxidative stress responsive serine rich 1 antisense RNA 1 (OSER1-AS1) in peripheral blood of patients with NSCLC. OSER1-AS1 in peripheral blood of patients with lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and healthy subjects was detected, and the clinical diagnostic efficacy was analyzed. The correlation between OSER1-AS1 expression and clinicopathological features in patients with LUSC and LUAD was analyzed. The downstream mechanism of OSER1-AS1 was explored. The area under the ROC curve of lncRNA OSER1-AS1 and miR-1298-5p/CHSY3 in LUSC and LUAD was compared using the MedCalc analysis. OSER1-AS1 was low in peripheral blood of patients with LUSC and LUAD. The area under the ROC curve for predicting LUSC was 0.800. The area under the ROC curve for predicting LUAD was 0.728. In LUSC and LUAD, OSER1-AS1 deficiency was associated with tumor node metastasis stage, lymph node metastasis, distal metastasis, and poor prognosis. miR-1298-5p was highly expressed, while chondroitin sulfate synthase 3 (CHSY3) was lowly expressed in patients with LUSC and LUAD. miR-1298-5p had target relations with OSER1-AS1 and CHSY3. lncRNA OSER1-AS1 had a higher diagnostic value in patients with NSCLC than miR-1298-5p and CHSY3. Overall, low expression of OSER1-AS1 in peripheral blood of NSCLC patients has high clinical significance, which provides a certain reference value for NSCLC early diagnosis.

Topics: Carcinoma, Non-Small-Cell Lung; Chondroitin Sulfates; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MicroRNAs; RNA, Antisense; RNA, Long Noncoding; Serine

Cationic antimicrobial peptides (CAPs) with antitumor activity have potential for use as novel antitumor agents because of their lower risk for induction of resistance. Of these peptides, magainin II (MG2) exhibited cytotoxicity in tumor cells only at high concentrations, likely due to the inefficiency of MG2 in cell membrane binding and cell entry. Conjugation to a cell-penetrating peptide (CPP) might enhance the cytotoxicity of MG2 in tumor cells. Here, we constructed a fusion peptide MG2A by conjugating MG2 to the N-terminus of the CPP penetratin (Antp). It was found that the fusion peptide MG2A is more potent than unconjugated MG2 at tumor cell killing. The IC50s of MG2A for the tumor cells tested were at least 30 times lower than the IC50s of unconjugated MG2. These data indicate that conjugation to Antp significantly enhanced the cytotoxicity of MG2 in tumor cells. Moreover, the IC50s of MG2A for tumor cells are within 2 to 3 μM, which are about three to five times lower than the IC50 for normal cells. Furthermore, chondroitin sulfate (CS) was found to be overexpressed on the surface of the tested tumor cells, and the cytotoxicity of MG2A could be inhibited by the addition of exogenous CS. These results suggest that binding of Antp to CS on tumor cells might be one important cause for the selective cytotoxicity of MG2A in tumor cells. Taken together, conjugation of MG2 to Antp can significantly enhance its antitumor activity, and the fusion of CAP to Antp might be an alternative for cancer-targeted therapy.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Carrier Proteins; Caspases; Cell Survival; Cell-Penetrating Peptides; Central Nervous System Neoplasms; Chlorocebus aethiops; Chondroitin Sulfates; Drug Carriers; Glioma; HeLa Cells; Humans; Inhibitory Concentration 50; Kidney Tubules, Proximal; Lung Neoplasms; Magainins; Melanoma; Molecular Targeted Therapy; Neoplasms; Rats; Skin Neoplasms; Vero Cells; Xenopus Proteins