Objective To review the application advancements of ATP-binding cassette (ABC) transporter in medical research.Methods Relevant literatures about the applications of ABC families in medical research were reviewed. Results ABC families mainly took roles in transporting substances across cell membrane. Some of them were useful for the prediction of drug resistance and the prognosis of malignant tumors. Others were target s for molecular researches. Their expressions or mutations might be related with the occurrence of diseases. Conclusion ABC families are very important in the diagnosis and therapy for diseases. Thus they are very promising tools for future medical research.
Bone malignancies exhibit the characteristics of high incidence, poor prognosis, and strong chemoresistance. Exosomal microRNAs can regulate the proliferation of bone malignant cells, improve chemoresistance, influence cell communication and the microenvironment, and have significant potential in the diagnosis and treatment of bone malignancies. Due to their stability, exosomal microRNAs can serve as non-invasive biomarkers for diagnosis and prognosis. However, their widespread application in clinical settings requires standardized research. This review summarizes the progress of exosomal microRNA research in various bone malignancies including osteosarcoma, chondrosarcoma, Ewing sarcoma, and fibrosarcoma, to provide new theoretical foundations and perspectives for the field.
ObjectiveTo summarize the latest advances in copper and cuproptosis in the field of breast cancer, and to provide a reference for clinical treatment decisions. MethodThe literatures related to copper and cuproptosis in recent years were read and summarized, and the research progress on the role of copper in breast cancer, the application of cuproptosis in the diagnosis and treatment of breast cancer were reviewed. ResultsCuproptosiswas a novel form of programmed cell death, which occurred via direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle, this resulted in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, leading to proteotoxic stress and ultimately cell death. Cuproptosis induced proliferation and migration of breast cancer cell , mediated personalized immunotherapy, and participated in endocrine and chemotherapeutic drug resistance. ConclusionExploring the mechanism of cuproptosis provides potential applications for subsequent immunotherapy, endocrine therapy, and chemotherapy for breast cancer, leading to new effective strategies for patients.
Objective To study the effects of survivin antisense RNA on SGC7901 cell’s apoptosis and chemosensitivity to taxotere, and to investigate its effect on the expression of multi-drug resistance gene-1 (MDR-1). Methods Survivin antisense eukaryotic vector anti-pcDNA3-svv was transfected into SGC7901 cell lines by lipofectamine and positive clones were screened out then. Survivin protein and MDR-1 mRNA were measured by western blot and RT-PCR, respectively. Apoptosis that was induced by anti-pcDNA3-svv was observed by electronic microscope, and the sensitivity of SGC7901 cell to taxotere was examined by MTT. Results The expressions of survivin protein and MDR-1 mRNA in transfected SGC7901 cells both decreased more significantly than that of non-transfected cells (P＜0.05， P＜0.01), and the indices of MDR of transfection group and non-transfection group were 0.196±0.013 and 3.126±0.019, respectively, at the late phase of apoptosis, which had a significant difference between each other (P＜0.01), IC50 of the transfected cells to taxotere was （16.7±1.98） ng/ml and that of the non-transfected cells was (55.7±1.89) ng/ml, which also had a significant difference (P＜0.01). Conclusion Surivivin antisense RNA could induce the apoptosis of SGC7901 cancer cell line and could increase the cells’ sensitivity to taxotere, which may help to reverse drug resistance.
ObjectiveTo investigate the molecular mechanism by which metastasis-associated protein 3 (MTA3) participates in glioma resistance through reactive oxygen species. Methods Protein expression in glioma stem cells (GSCs) and non-GSCs was detected using Western blotting. GSCs included U87 and SHG44 cells, while non-GSCs included U87s and SU-2 cells. After overexpressing MTA3, U87 and SHG44 cells were divided into Lv-scr and Lv-MTA3 groups. The self-renewal capacity of glioma cells was assessed through a neurosphere formation assay. Cell survival fractions were examined following exposure to 0, 2, 4, 6, 8, and 10 Gy X-ray irradiation under normoxic or hypoxic conditions. Apoptosis and reactive oxygen species expression were analyzed using flow cytometry. Immunofluorescence staining was performed to detect the stem cell markers CD133 and nestin, as well as the differentiation markers glial fibrillary acidic protein (GFAP, for astrocytes) and neuronal class Ⅲ β-tubulin. Results In GSCs, MTA3 expression was lower in the U87s and SU-2 groups. After MTA3 overexpression, Lv-MTA3 expression was higher in U87s and SU-2 compared to the Lv-scr group. Under normoxic or hypoxic conditions, U87 and SU-2 showed greater radioresistance compared to glioma cell lines U87 and SHG44. Compared to non-GSCs, basal reactive oxygen species formation was reduced in GSCs, while reactive oxygen species generation was increased in non-GSCs. Following exposure to different doses of X-rays under normoxic or hypoxic conditions, GSCs with MTA3 overexpression exhibited greater radiosensitivity than those with stable integration. Additionally, MTA3 overexpression slightly increased the oxygen enhancement ratio (OER) in GSCs. MTA3 overexpression reduced the immunoreactivity of CD133 and nestin in both stem cell lines, and increased immunofluorescence staining of GFAP and neuronal class Ⅲ β-tubulin, with statistically significant differences (P<0.05). Conclusions MTA3 is downregulated in GSCs. Overexpression of MTA3 reduces the radioresistance and stemness of GSCs both in vitro and in vivo. MTA3 plays a crucial role in regulating the radiosensitivity and stemness of GSCs through reactive oxygen species.
ObjectiveTo summarize the recent advances in the relationship between long non-coding RNA (LncRNA) and tumor autophagy, autophagy and drug resistance regulation.MethodsReviewed the relevant literatures at home and abroad, and reviewed the recent research progress of LncRNA regulation of autophagy to affect tumor resistance.ResultsDrug resistance was a common problem in the process of anti-tumor therapy. Autophagy played an important role in the process of tumor resistance as an important mechanism to maintain cell homeostasis. Abnormal regulation of LncRNA could contribute to the occurrence and development of tumors, and could also mediate the resistance of tumor cells to anti-tumor drugs by promoting or inhibiting autophagy.ConclusionsLncRNA can mediate tumor autophagy in a positive or negative direction, and autophagy is a " double-edged sword” for tumor resistance. LncRNA may improve tumor resistance to drugs by regulating autophagy.
【Abstract】 Objective To detect the expression of lung resistance protein (LRP) and investigate its significance in pancreatic carcinoma cell lines (SW1990, PCT-2, PCT-3, PCT-4, Aspc-1, Capan-1, Mia-PaCa-2 and Panc-1). Methods Reverse transcription PCR (RT-PCR) and immunocytochemistry (ICC) were carried out to investigate the expression of LRP. Results LRP mRNA was absent in PCT-2 cell line by RT-PCR. Mild to moderate expression level was found in other pancreatic carcinoma cell lines. PCT-4, Aspc-1 and Panc-1 presented the highest LRP mRNA expression level, in contrast, SW1990, PCT-3, Capan-1 and Mia-PaCa-2 showed moderate LRP mRNA expression. The median value was 0.56±0.33. LRP was further validated by ICC. Absent to weak protein expression of LRP was found in PCT-2 and PCT-3. Overexpressed LRP was present in SW1990, Capan-1 and Aspc-1, furthermore, the highest expression of LRP was found in Panc-1, Mia-PaCa-2 and PCT-4 cell lines. Conclusion All these data showed that LRP might play an important role in multidrug resistance of pancreatic carcinoma.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.
ObjectiveTo establish multidrugresistance cell substrain of human hepatocellular carcinoma and to investigate its characteristics.MethodsSMMC7721 cell strain was cultured in Adriamycin(ADM). The multidrugresistance cell substrain SMMC7721/ADM was harvested after a long period of culture by gradually increasing the concentration of ADM and its characteristics were investigated. Results①The drug resistance of SMMC7721/ADM to ADM increased by 33.3 times, to Vincristine 16.8 times, to Diamminedichloroplatinum 2.8 times. ②The drug resistance cell substrain had almost the same growth velocity as its parental generation. The doubling time was 32.0 hours and 30.5 hours respectively. They had the analogous growth curves. ③The obvious difference between the drug resistance cell substrain and its parental generation was that the former’s microvilli became thick, short and scattered by scanning and transmitting electron microscopy. ④The multidrug resistance cell substrain kept the characteristics of hepatocellular carcinoma, it could be transplanted into the subcutaneous tissue of nude mice. ⑤The drug resistance of the cell substrain reduced to 28.0% and 9.2%after removal of the drug for 1 month and 2 months respectively, its drug resistance could remain stable (35.4 times) after 2 months of culture in ADM (0.04 μg/ml).ConclusionThe SMMC7721/ADM cell substrain has the stable fundamental characteristics of a drug resistance cell strain.
Objective To investigate the effect of phosphorothioate antisense oligonucleotides(AS-ODN) on suppressing multidrug resistance-associated protein gene(MRP) in human drug-resistant hepatocellular carcinoma cell line (SMMC-7721/ADM). Methods Cell line was transfected with a synthetic S-ODN complementary to the coding region of MRP mRNA, Lipofectamine acting as carrier. The drug sensitivity was measured by MTT assay. The expression of MRP mRNA was detected by RT-PCR and the expression of P190 was detected by flow cytometry. Results AS-ODN inhibited expression of MRP mRNA and P190 and promoted sensitivity to daunorubicinum and adriamycinum. Conclusion AS-ODN can reduce the expression of MRP gene. MDR caused by MRP is an important cause of multidrug resistance of SMMC-7721/ADM.