Long non-coding RNA SSTR5-AS1 facilitates gemcitabine resistance via stabilizing NONO in gallbladder carcinoma.

Gallbladder carcinoma (GBC) is the most aggressive carcinoma of the biliary tract, effective chemotherapy was critical for the patients with unresectable GBC. However, chemotherapy resistance is still problematic for clinicians. Here, we identified a specific long non-coding RNA, SSTR5-AS1, in GBC patient that facilitates gemcitabine resistance. SSTR5-AS1 is significantly increased in GBC samples and cell lines, especially in gemcitabine-resistant cell lines, and higher SSTR5-AS1 expression was correlated with poorer overall survival rate in GBC patients. Our data revealed that upregulated SSTR5-AS1 facilitates gemcitabine resistance via inhibiting apoptosis. Knockdown of SSTR5-AS1 sensitized drug resistant GBC cells to gemcitabine in vitro and strongly inhibited xenografts formed by drug resistant GBC cells in vivo. Moreover, we found via streptavidin pull down assay that NONO specifically binds to sense sequence of SSTR5-AS1 and prevented proteasome mediated NONO degradation, which resulted in increased NONO protein level without affecting the transcription of NONO. NONO functions as the downstream effector of SSTR5-AS1 and is required for SSTR5-AS1 mediated gemcitabine resistance. Collectively, our data provided novel insights into lncRNA-mediated chemotherapy resistance and suggested a novel therapeutic target to improve chemotherapy strategies for unresectable GBC patients.

Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation.

Triptolide exhibits immunosuppressive, anti-inflammatory, antifertility and antineoplastic functions. However, the anticancer effect of triptolide on cervical cancer and the underlying mechanism remains to be fully understood. The present study assessed the mechanisms underlying the effect of triptolide on the viability and apoptosis of human cervical cancer cells. SiHa cells were treated with 12.5-100.0 nM triptolide for 12, 24 or 48 h. The present study demonstrated that triptolide inhibited viability and induced apoptosis in SiHa cells time- and dose-dependently. Furthermore, treatment with triptolide promoted autophagy and activated microtubule associated protein 1 light chain 3 α expression in SiHa cells. Triptolide treatment suppressed the expression of phosphorylated (p)-protein kinase B (Akt), p-mechanistic target of rapamycin (mTOR), and p-p70S6K, activated the expression of p-p38, mitogen-activated protein kinase (MAPK) and p53 and inhibited the expression of p-forkhead box O3 (Foxo3a) in SiHa cells. These results suggested that triptolide induces protective autophagy, suppresses cell viability and promotes apoptosis in human cervical cancer cells by inducing the autophagy-targeting phosphoinositide 3-kinase/Akt/mTOR, p38, MAPK, p53 and Foxo3a pathways.

Effect of allyl isothiocyanate on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro.

The present study aimed to investigate the effect of allyl isothiocyanate (AITC) on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro, and to explore the potential underlying mechanisms of this. HeLa cells were treated with varying concentrations of AITC for different durations. The cell viability was then measured using a Cell Counting kit-8 assay and the apoptosis rate of the cells was detected using flow cytometry. Additionally, the B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA expression levels were determined by reverse transcription-quantitative polymerase chain reaction, while the Bax and Bcl-2 protein expression levels in cells were detected by western blot analysis. AITC was revealed to inhibit the viability of HeLa cells. AITC was revealed to induce the apoptosis of HeLa cells, as the apoptosis rate increased gradually with an increase in the dose. As the concentration of AITC increased, the Bax mRNA expression level increased, whilst the Bcl-2 mRNA expression level decreased. Furthermore, the Bax protein expression intensity increased whilst Bcl-2 protein expression intensity decreased, thereby resulting in a decrease in the ratio of Bcl-2/Bax proteins. AITC may inhibit cell viability by inducing the apoptosis of HeLa cells and this may be accounted for by the imbalance in the Bcl-2/Bax expression ratio.

The comparison of coronary angiographic profiles between diabetic and nondiabetic patients with coronary artery disease in a Chinese population.

BACKGROUND: It is well known that diabetes mellitus (DM) is a crucial risk factor for coronary artery disease (CAD). The present study aimed to investigate angiographic profiles of the coronary arteries in diabetic CAD patients in comparison with nondiabetics. METHODS: A total of 546 Chinese patients were angiographically documented for CAD, 375 of whom were diabetics and 171 were nondiabetics according to the WHO diabetes criteria (1999). The patients in these two groups were matched for age, sex, and body mass index (BMI). The 75 g oral glucose tolerance test (OGTT) was performed in all patients, for whom blood glucose, insulin, glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] were measured. Insulin resistance (Homa-IR) and insulin secretion index (Homa-IS) were determined by the HOMA model. The clinical features and the data from selective coronary angiographies were compared between the diabetic and nondiabetic CAD patients. RESULTS: Diabetic CAD patients had significantly higher waist to hip ratio (WHR) (p=0.016), fasting plasma glucose (FPG), 2h plasma glucose (2hPG), glycosylated hemoglobin (HbA1c) (p<0.001), insulin resistance index (Homa-IR) (p=0.001), and apolipoprotein A (ApoA) (p=0.008), with a significantly lower insulin secretion index (Homa-IS) level (p<0.001). Diabetic patients had one-vessel disease less frequently (28.8% vs 46.2%, p<0.001), and three-vessel disease more frequently (35.2% vs 24.0%, p=0.009), and they also had significantly higher cumulative coronary atherosclerosis score (CAS) (p=0.003). The right coronary artery was significantly more frequently involved in diabetics (66.4% vs 52.6%, p=0.002), with a clearly higher CAS at the same time (p=0.002). CONCLUSIONS: Diabetics were presented with more severe and diffuse angiographically documented coronary artery disease compared to nondiabetics. The right coronary artery was significantly more frequently involved in the diabetics. Duration of CAD, Homa-IR, and diabetes mellitus were the independent risk factors for CAD found in the present study, while ApoA was the protective one.