ABSTRACT
OBJECTIVE@#To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms.@*METHODS@#We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor).@*RESULTS@#In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis.@*CONCLUSIONS@#ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.
Subject(s)
Female , Humans , Acetates , Pharmacology , Apoptosis , Genetics , Autophagy , Autophagy-Related Proteins , Metabolism , Benzopyrans , Pharmacology , Breast Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Gene Expression Regulation , MCF-7 Cells , Morpholines , Pharmacology , Proto-Oncogene Proteins c-akt , Metabolism , Pyrans , Pharmacology , TOR Serine-Threonine Kinases , Metabolism , Triazines , Pharmacology , Ubiquitin-Conjugating Enzymes , MetabolismABSTRACT
ObjectiveTo evaluate the efficacy of radical transurethral bladder tumor resection plus chemotherapy for the treatment of muscle-invasive bladder cancer. Methods Thirty-two patients,who were diagnosed muscle-invasive bladder cancer by preoperative CT and cystoscopy and not tolerating or rejecting radical cystectomy were treated by transurethral resection of bladder tumor (TURBt).The maximum diameter of tumor ranged from 1 - 5 cm,3 cm on average.After conventional intravenous chemotherapy ( docetaxel 75 mg/m2 + oxaliplatin 130 mg/m2),and given intravenous therapy (HCPT 20 mg + 20 ml saline).Regular cystoscopy was used to monitor tumor recurrence.The examination was performed quarterly in the first 2 years post operation,twice a year since the third year.ResultsThe tumors of 32 cases were resected completely.Operative time were 15 -70 min,the blood loss was 10 -150 ml,without serious complications during the operation.Pathological report showed 32 cases of transitional cell carcinoma.Clinical stages were T2a 20 cases,T2b 12 cases.Pathological grade were G2 13 cases,G3 19 cases.There was no bone marrow suppression,anemia or other severe complications was seen in 32 cases that received chemotherapy.3 of which manifested as low fever,mild nausea,and headache,respectively,having a rest 2 to 3 days the symptoms disappeared.32 patients were followed up for 3 - 60 months,a mean of 28 months.After 1 year the recurrence rate was 9.4％ (3/32),after 2 years was 12.5％ (4/32).The TNM stage of these recurrence cases were 4 cases with T2a and 3 cases with T2b.12 patients died,5 patients died of bladder cancer metastasis.Other 20 patients were survival with no recurrence.ConclusionRadical TURBt plus chemotherapy could be a treatment for the selected patients with muscle invasive bladder cancer.
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Objective To study the relationship of HHV-8 K15 allelotypes in cutaneous and esophageal squamous cell carcinoma(SCC) tissue with tumorigenesis. MethodsSequence specific primernested PCR was performed to detect HHV-8 K15 gene and to determine its allelotype in paraffin-embedded tissue specimens from 40 patients with cutaneous SCC and 40 patients with esophageal SCC. Chi-square test was used for statistical analysis. ResultsHHV-8 K15 P allele was detected in 9(22.5％) of the cutaneous SCC specimens and 8(20％) of the esophageal SCC specimens. There was no significant difference in the detection rate of HHV-8 between cutaneous SCC and esophageal SCC specimens (P ＞ 0.05). HHV-8 K15 M allele was undetected in this study. ConclusionsSCC tissues appear to harbor only HHV-8 K15 P allele, and HHV-8 may play a part in the initiation and progression of SCC.