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Wen-Yan Wang,1,2Yun-Xia Cao,2 Xiao Zhou,3 Bing Wei11Department of Obstetrics and Gynecology, The Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 2Teaching and Research Group of Obstetrics and Gynecology, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of ChinaIntroduction: In this study, novel folic acid (FA)-modified curcumin (CUR) liposomes (LPs) were developed and evaluated for their antitumor activity in vitro and in vivo.Methods: Characterization of the LPs, including transmission electron microscopy, morphology, particle size, and zeta potential studies, was carried out. Drug entrapment efficiency, drug-loading capacity, and release properties in vitro were tested. The in vitro growth inhibition activity, cellular uptake efficiency, and cell apoptosis of FA-modified CUR LPs were also investigated by a cervical cancer HeLa cell model.Results: The optimized distearoyl-l-a-phosphatidylethanolamine (DSPE)-PEG2000-FA-LPs/CUR formed spherical vesicles of nanometer sizes and had particle sizes of 112.3±4.6 nm, polydispersity index of 0.19±0.03, and zeta potential of −15.3±1.4 mV. In addition, the EE% and DL% of (DSPE)-PEG2000-FA-LPs/CUR were 87.6% and 7.9%, respectively. Compared with the free drug, FA-modified CUR LPs had sustained-release properties in vitro. In vivo, a strong green fluorescence was observed in the cytoplasmic region after incubation of (DSPE)-PEG2000-FA-LPs/CUR for 2 hrs.Conclusion: (DSPE)-PEG2000-FA-LPs/CUR showed a superior antiproliferative effect on HeLa cells and had a better antitumor effect in vivo than the non-modified LPs. These results indicated that (DSPE)-PEG2000-FA-LPs/CUR was a promising candidate for antitumor drug delivery.Keywords: curcumin, folic acid, liposome, release, cell uptake, antiproliferative, antitumor study, HeLa

Many cervical cancer (CC) patients suffer from cancer invasion and lymph node metastasis, resulting in poor therapeutic outcome. Evidence has indicated the involvement of misexpressed high-mobility group AT-hook 2 (HMGA2) in poor survival of cancer patients. This study hereby aims to investigate the role of HMGA2 in CC cell biological functions via the ATR/Chk1 signaling pathway. The cell line with the highest HMGA2 expression was selected to establish cell lines with wild-type and stable HMGA2 silencing. The underlying regulatory mechanisms of HMGA2 in CC cells were analyzed with the treatment of the ATR/Chk1 signaling pathway activator, inhibitor, shRNA against HMGA2 or pcDNA-HMGA2 plasmids, followed by quantification of expression levels of ATR, Chk1, Bcl-2, Bax, MMP-2, MMP-9, E-cadherin and N-cadherin. CC cell apoptosis, proliferation, migration, invasion and lymph node metastasis in nude mice were evaluated. The HeLa cell line with the highest HMGA2 expression was selected. HMGA2 inhibited the activation of the ATR/Chk1 signaling pathway. Notably, HMGA2 silencing or inhibition of the ATR/Chk1 signaling pathway inhibited epithelial mesenchymal transition (EMT), CC cell proliferation, invasion, migration, tumorigenicity and lymph node metastasis while promoting apoptosis, indicated by reduced expression of Bcl-2, MMP-2, MMP-9 and N-cadherin, with increased expression of E-cadherin and Bax. Collectively, our study provides evidence that HMGA2 gene silencing inhibits the activation of the ATR/Chk1 signaling pathway, whereby repressing EMT, proliferation, migration and invasion of CC cells and lymph node metastasis, and promoting CC cell apoptosis.

Background: Circular RNAs (circRNAs) as a new class of non-coding RNAs that are associated with cancer progression and can serve as potential markers for cancer diagnosis. However, the functions of circRNAs have not been completely clarified in non-small-cell lung cancer (NSCLC). Our study aimed to explore the expression profiles and apoptotic role of circRNAs in NSCLC. Methods: Forty-one NSCLC patients and twenty-six healthy subjects were recruited to our study. The levels of hsa_circ_0102533 in tumor tissues and whole blood were identified by circRNA microarray and RT-qPCR. The CCK-8 and apoptosis assays were performed in NSCLC cell lines after they were transfected with si-circRNA and si-NC. Results: Compared with the control group, hsa_circ_0102533 expression was significantly increased in tumor tissues and whole blood from NSCLC patients. ROC analysis showed that hsa_circ_0102533 had a higher diagnostic power for the detection of cancer in stage I-II NSCLC patients [AUC: 0.774 (95% CI: 0.624-0.923)] than in stage III-IV NSCLC patients [0.728 (95% CI: 0.588-0.869)]. Furthermore, the knockout of hsa_circ_0102533 by siRNA significantly inhibited proliferation and induced apoptosis in NSCLC cell lines. Conclusion: Hsa_circ_0102533 possesses an oncogenic property in the carcinogenesis of NSCLC and might be an early diagnostic biomarker for NSCLC detection.