Abstract BackgroundHepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant tumors in the world, and its recurrence and mortality rate are still in high level. In recent years, more and more inhibitors against gene targets have been found to be beneficial to survival. However, the function of homo-sapiens histone H3 associated protein kinase (GSG2) in HCC has not been completely understood. MethodsThe expression of GSG2 in HCC tissues was detected by immunohistochemical staining. The lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown GSG2 expression in HCC cell lines Hep3B2.1-7 and SK-HEP-1. Cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively, and flow cytometry assay was used to investigate the cell apoptosis in vitro . Mice xenograft model was constructed to detect the functions of GSG2 on tumor growth in vivo . Human Apoptosis Antibody Array was conducted to find the possible mechanism.ResultsGSG2 was overexpressed in HCC tissues compared with adjacent normal tissues, which was positively related to the tumor pathological stage. The knockdown of GSG2 has the functions of inhibiting the progression of HCC, including inhibiting cell proliferation and colony formation and promoting cell apoptosis. Compared with shCtrl group, the shGSG2 group expressed higher apoptotic genes such as caspase 3, caspase 8, Fas and FasL, while lower IGF1, Bcl2 and Bcl-w. ConclusionsOur study showed that knockdown of GSG2 suppresses the tumor growth in vitro and vivo . Therefore, GSG2 might play an oncogenic role in HCC.
To improve the oral bioavailability of quercetin (Q) and achieve colon-specific release, a core–sheath electrospun fiber mat containing Q-loaded chitosan nanoparticle (Q-loaded EFM) was developed in this study. The nanoparticle was first fabricated, and its antioxidant activity was as effective as free Q. Then the uniform Q-loaded EFM was obtained using response surface methodology optimization, and its core–sheath structure was characterized by confocal laser scanning microscopy. In vitro release kinetics confirmed the colon targeting profile, and the release rate of Q varied inversely with fiber diameter. The data of Cell Counting Kit-8 suggested Q-loaded EFM inhibited the proliferation of Caco-2 cells in a dose- and time-dependent manner with an IC50 of 4.36, 2.81, and 2.01 mg/mL after 24, 48, and 72 h, respectively, and it was caused by arresting cell cycle on G0/G1 phase and triggering apoptotic cell death. This study suggests that the Q-loaded EFM represents a promising form in the oral therapy of colon disorders.
epithelium near the afferent side of the filament. Due to their identical size and location, histochemical (osmium-zinc iodide) and immunofluorescent (Na, K-ATPase) staining was used to demonstrate that these eosinophilic, Na, K-ATPase-immunoreactive (NKIR) cells are ionocytes. It is thus hard to examine the apical openings of ionocytes by scanning electron microscopy in the gill epithelium of the milkfish as compared to those in the other teleosts, because most ionocytes are distributed in the interlamellar regions of the filaments. Further confocal micrographs showed abundant NKIR cells on the filamental epithelia of both seawater- and freshwater-adapted fish. However, NKIR cells were rarely observed on the lamellar epithelia of gills in seawater-adapted individuals, while they were commonly found in freshwater-adapted milkfish. http://www.sinica.edu.tw/zool/zoolstud/43.4/772.pdf
The objective of this study was to determine the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC), thereby supplying a new insight for ccRCC treatment. Expression data in TCGA-KIRC were obtained. Target gene lncRNA for research was determined using expression analysis and clinical analysis. lncRNA's downstream regulatory miRNA and mRNA were predicted by bioinformatics databases. ccRCC cell malignant phenotypes were detected via CCK-8, colony formation, Transwell migration, and invasion assays. The targeting relationship between genes was assessed through dual-luciferase reporter gene analysis. Kaplan-Meier (K-M) analysis was carried out to verify the effect of MAGI2-AS3, miR-629-5p, and PRDM16 on the survival rate of ccRCC patients. MAGI2-AS3 expression in ccRCC tissue and cells was shown to be markedly decreased and its expression to continuously decline with tumor progression. MAGI2-AS3 suppresses ccRCC proliferation and migration. Dual-luciferase assay showed that MAGI2-AS3 binds miR-629-5p and that miR-629-5p binds PRDM16. In addition, functional experiments showed that MAGI2-AS3 facilitates PRDM16 expression by repressing miR-629-5p expression, thereby suppressing ccRCC cell aggression. K-M analysis showed that upregulation of either MAGI2-AS3 or PRDM16 significantly improves ccRCC patient survival, while upregulation of miR-629-5p has no significant impact. MAGI2-AS3 sponges miR-629-5p to modulate PRDM16 to mediate ccRCC development. Meanwhile, the MAGI2-AS3/miR-629-5p/PRDM16 axis, as a regulatory pathway of ccRCC progression, may be a possible therapeutic target and prognostic indicator of ccRCC.
Objective: To study the protective effect of Xinjiang Uighur Medicine Abnormal Savda Munziq and Mushil on hydrogen peroxide -induced cytotoxity in human lymphocyte. Methods: The inhibitory effect of hydrogen peroxide on cell growth was determined using the tetrazolium dye colorimetric test (MTT test). Results: H_2O_2 (800μmol/L) suppressed the growth of human lymphocyte and pre-incubation of the cell with Abnormal Savda Munziq (100 μg/L and 50 000 μg/L) reduced the suppression. Treatment of Abnormal Savda Mushil (100 μg/L to 50 000 μg/L) did not display significant effect on cell growth supression of the H_2O_2 induced cell group. Conclusions: Abnormal Savda Munziq has a strong protective ability against cytotoxity caused by hydrogen peroxide.
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis. Interestingly, PIP-platin can promote cell adhesion within several hours and the cells became hard to dislodge from the culture plate. A wound healing assay, transwell migration/invasion assay and 3D spheroid migration assay all demonstrated that PIP-platin can inhibit cell migration/invasion. To illustrate the associated mechanisms, we investigated the intracellular trafficking of β-catenin, a central protein in the regulation of cell adhesion, and gene transcription for cell proliferation. Upon treatment with PIP-platin, this protein can translocate onto the plasma membrane for increased cell adhesion. In addition, PIP-platin was demonstrated to efficiently inhibit Wnt signaling by blocking the translocation of β-catenin into the nuclei, thereby preventing cell proliferation. We demonstrate that, accordingly, PIP-platin has remarkable potential for intracellular delivery in mitochondria and has inhibitory effects on cancer cell proliferation and migration/invasion through β-catenin, and may therefore be exploited as a dual-functional antitumor drug candidate in cancer treatment.
Circular RNA (circRNA) hsa_circ_0077837 inhibits colorectal cancer. Our research studied the participation of hsa_circ_0077837 in non-small cell lung cancer (NSCLC). Hsa_circ_0077837 and phosphatase and tensin homolog (PTEN) expression in cancer and paired non-cancer tissues from a total of 64 NSCLC patients were studied with RT-qPCR. To evaluate the prognostic value of hsa_circ_0077837 for NSCLC, these 64 patients were monitored for 5 years. Expression of PTEN in NSCLC cells with hsa_circ_0077837 overexpression was determined by RT-qPCR and Western blot. The methylation of PTEN gene in cells transfected with hsa_circ_0077837 expression vector was analyzed by methylation specific PCR (MSP). The roles of hsa_circ_0077837 and PTEN in NSCLC cell proliferation were evaluated using cell apoptosis assay. Our data showed that hsa_circ_0077837 was upregulated in NSCLC and predicted poor survival. Besides, hsa_circ_0077837 expression level was higher in 36 advanced cases (stage III and IV) than in 28 early-stage cases (stage I and II). Hsa_circ_0077837 was inversely correlated with PTEN across cancer tissues. In NSCLC cells, hsa_circ_0077837 overexpression decreased PTEN expression, increased PTEN gene methylation, and reduced HCC827 cell apoptosis via PTEN. Overall, hsa_circ_0077837 is upregulated in NSCLC and downregulates PTEN by increasing its gene methylation to suppress cell apoptosis.List of abbreviations:Non-small cell lung cancer (NSCLC); circRNAs (circular RNAs); methylation-specific PCR (MSP).
Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy as it has unique capacity to selectively trigger apoptosis in cancer cells. We reported here that paclitaxel sensitized gastric cancer cells to TRAIL-induced apoptosis. Methods: After drug exposure, apoptosis rate and caspase activation were examined. Various proteins were detected by western blot. Several interventions, including pharmacological inhibitors and siRNA transfection were used. The growth inhibition of tumors was evaluated in SGC- 7901-implanted nude mice model. Results: We found gastric cancer cellsshowed a mixed response to TRAIL. Combined treatment with paclitaxel markedly enhanced TRAIL-induced apoptosis in vitro and in vivo. The underlying mechanisms involved in synergistical activation of caspase proteins, upregulation of receptors, down-regulation of antiapoptotic proteins and inactivation of MAPKs. Conclusion: TRAILinduced cytotoxicity and apoptosis can be synergistically enhanced by paclitaxel, suggesting the therapeutic potential of combining TRAIL plus paclitaxel in gastric cancer treatment.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)