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Severe side effects are major problems with chemotherapy of gastric cancer (GC). These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), cisplatin (DDP), or cyclophosphamide (CTX) to treat GC cells. Combined effectiveness of GLB with drugs was determined by proliferation assay. The molecular mechanisms associated with cell proliferation, migration, invasion, cell cycle, DNA repair/replication, apoptosis, and autophagy were investigated by immunoblotting for key proteins involved. Cell cycle and apoptosis analysis were performed by flow cytometry. Reactive oxygen species level was also examined for identification of its role in apoptosis. Proliferation assay revealed that the addition of 5 µM GLB significantly sensitizes gastric cancer SGC-7901 cells to MMC, DDP, and CTX by decreasing half-maximal inhibitory concentration (IC 50 ) by up to 75.40%±5%, 45.10%±5%, and 52.10%±5%, respectively. GLB + drugs decreased the expression level of proteins involved in proliferation and migration, suggesting the anticancer potential of GLB + drugs. GLB + MMC, GLB + CTX, and GLB + DDP arrest the cells in G 0 /G 1 and G 1 /S phase, respectively, which may be the consequence of significant decrease in the level of enzymes responsible for DNA replication and telomerase shortening. Combined use of GLB with these drugs also induces DNA damage and apoptosis by activating caspase/PARP pathways and increased production of reactive oxygen species and increased autophagy in GC cells. GLB dosage sensitizes GC cells to the alkylating agents via arresting the cell cycle and enhancing cell death. This is of significant therapeutic importance in the reduction of side effects associated with these drugs., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Chemotherapy is an important treatment for cancer patients, especially for those with unresectable lesions. Targeted therapy of cancer by specific inhibition of aberrant tyrosine kinase activities in cancer cells with chemically synthesized tyrosine kinase inhibitors (TKIs), shows better responses while less side effects than traditional chemotherapeutic drugs. It is common that cancer cells often exhibit deregulation of several tyrosine kinases simultaneously, multikinase TKIs (MKIs) therefore have greater advantages over single-target TKIs. Currently more MKIs are under developing for better efficacy for different types of cancer. In the present work, we evaluated the in vitro therapeutic potential of a novel MKI, namely R8, with comparison to the clinically available MKI Sunitinib. Results showed that R8 has stronger inhibition on six different types of cancer cell lines with lower IC 50 than Sunitinib does. Cell cycle analysis showed that R8 induced significant G0/G1 arrest phase of lung cancer A549 and NCI-H226 cells. The inhibition was also confirmed by colony formation and migration assays in both lung cancer cell lines in a dose-dependent manner. R8 could significantly inhibit the phosphorylation of multiple receptor tyrosine kinases (RTKs) included PDGFRβ, VEGFR2, EGFR and C-Kit, leading to the down-regulation of PI3K-Akt-mTOR signaling. Further analysis revealed that R8 treatment induced more significant apoptosis than Sunitinib did, which might be the consequence of the autophagic cell death. In conclusion, this work suggested R8 to be a promising novel anticancer MKI, and provided the basis for further in vivo investigation on its potential in treatment of lung cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Objective: To investigate the effect of chronic exposure to sodium arsenite at a dose of 1. 0 μmol / L on proliferation of human bronchial epithelial cells( HBE) and human keratinocytes( HaCaT) and discuss the mechanism of arsenic carcinogenesis., Methods: Malignant transformation model of HBE and HaCaT cells cultured in vitro were used in this study. MTT assay was used to detect the capacity of proliferation. Flow cytometry was used to detect cell cycle. The expression of cell cycle related protein like cyclin E, cyclin D1 and cyclin A protein were inspected by Western blot., Results: The treated cells, including passage 36 and 43 of HBE cells and passage 28 and 35 of HaCaT cells grow faster than the control group( P < 0. 01 and P < 0. 05). The treated cells in the G1 phase were decreased( P < 0. 05), however cells in the S phase were increased( P <0. 05). In addition, the expression of cyclin E displayed a trend of up-regulation( P <0. 05), and it was maintained at a high level in advanced period., Conclusion: By increasing the expression of cyclin E in HBE and HaCaT cells, low dose of sodium arsenite made cells escaping from the G1 phase to S phase, accelerating cell cycle progression and proliferation, a way that may lead to malignant transformation.

Objective: To establish the human colorectal cancer cell model SW620/PAR4D with inducible suppression of proteinase activated receptor 4 (PAR4) expression, and investigate the role PAR4 plays in the proliferation and migration of cancer cells., Methods: A human colorectal cancer cell line with tetracycline-inducible expression regulatory system, namely SW620/Tet-on, was established; inducible expression lentiviral vector with artificial microRNA targeting PAR4, pLVX-Tight-Puro-PAR4-miR, was constructed and transfected into SW620/Tet-on to make an inducible PAR4-suppressed cell model SW620/PAR4D. Western blotting was used to confirm the suppression of PAR4 expression after the doxycycline (DOX) treatment. CCK-8 assay was used to evaluate the impact of suppressed PAR4 expression on cell proliferation, and wound-healing assay was used to analyze the migration of the cells., Results: The SW620/PAR4D cell model was established successfully. Suppression of PAR4 expression by DOX treatment had no significant impact on the growth/proliferation of SW620/PAR4D cells, but markedly inhibited the cell migration., Conclusion: Suppression of PAR4 expression has no significant effect on the proliferation of SW620 cells, but can inhibit the migration of the cells.

Well dispersed 45S5 Bioglass(®) (BG)-graphene nanoplatelets (GNP) composites were prepared after optimising the processing conditions. Fully dense BG nanocomposites with GNP loading of 1, 3 and 5 vol% were consolidated using Spark plasma sintering (SPS). SPS avoided any structural damage of GNP as confirmed using Raman spectroscopy. GNP increased the viscosity of BG-GNP composites resulting in an increase in the sintering temperature by ~50 °C compared to pure BG. Electrical conductivity of BG-GNP composites increased with increasing concentration of GNP. The highest conductivity of 13 S/m was observed for BG-GNP (5 vol%) composite which is ~9 orders of magnitude higher compared to pure BG. For both BG and BG-GNP composites, in vitro bioactivity testing was done using simulated body fluid for 1 and 3 days. XRD confirmed the formation of hydroxyapatite for BG and BG-GNP composites with cauliflower structures forming on top of the nano-composites surface. GNP increased the electrical conductivity of BG-GNP composites without affecting the bioactivity thus opening the possibility to fabricate bioactive and electrically conductive scaffolds for bone tissue engineering.