Sensitization of cancer cells to paclitaxel-induced apoptosis by canagliflozin.

Cancer cells consume more glucose and usually overexpress glucose transporters which have become potential targets for the development of anticancer drugs. It has been demonstrated that selective SGLT2 inhibitors, such as canagliflozin and dapagliflozin, display anticancer activity. Here we demonstrated that canagliflozin and dapagliflozin synergistically enhanced the growth inhibitory effect of paclitaxel in cancer cells including ovarian cancer and oral squamous cell carcinoma cells. Canagliflozin also inhibited glucose uptake via GLUTs. The combination of paclitaxel and WZB117, a GLUT inhibitor, exhibited a strong synergy, supporting the notion that inhibition of GLUTs by canagliflozin may also account for the synergy between canagliflozin and paclitaxel. Mechanistic studies in ES-2 ovarian cancer cells revealed that canagliflozin potentiated paclitaxel-induced apoptosis and DNA damaging effect. Paclitaxel in the nanomolar range elevated abnormal mitotic cells as well as aneuploid cells, and canagliflozin further enhanced this effect. Furthermore, canagliflozin downregulated cyclin B1 and phospho-BUBR1 upon spindle assembly checkpoint (SAC) activation by paclitaxel, and may consequently impair SAC. Thus, paclitaxel disturbed microtubule dynamics and canagliflozin compromised SAC activity, together they may induce premature mitotic exit, accumulation of aneuploid cells with DNA damage, and ultimately apoptosis.

Effect of different treatments of highly translucent zirconia on the bonding strength between zirconia and veneering porcelain / 口腔疾病防治

Objective @# To evaluate the effect of different surface treatments on the bonding strength between highly translucent zirconia and veneering porcelain and to provide a research basis for improving the zirconium porcelain bond strength between zirconium and ceramic material.@*Methods @# Thirty cylindrical zirconia blocks with 10-mm diameter and 10-mm height were prepared and divided into four groups (n=7), labeled as control group (C), sandblasting group (S), bonding group (B), and sandblasting and bonding group (SB). The surface morphology of zirconia before and after sandblasting was observed in the remaining two specimens. Group C was veneered (2 mm in height and 5 mm in diameter) with porcelain powder by layering after grinding. Group S was sandblasted after grinding. Group B was veneered with a thin layer of porcelain powder as bond coating. Group SB was sandblasted and veneered with a thin layer of porcelain powder. After sintering, the shear specimens were embedded, and a shear bond strength test was conducted. Statistical analysis was conducted to analyze the data. Fracture surface analysis was also performed to determine the failure modes by stereomicroscopy.@*Results @# The bonding strength of group C was 21.86 ± 3.18 MPa. For group S, it was 22.12 ± 3.06 MPa. For group B, it was 19.19 ± 1.46 MPa. Finally, for group SB, it was 27.76 ± 1.95 MPa. There was no significant difference in shear strength between group C, group S and group B. There was a significant difference in shear strength between each group and group SB (P < 0.05). Under a stereomicroscope, the observed fracture modes of each group were mainly mixed failure.@*Conclusion@#Sandblasting cannot significantly increase the bonding strength between zirconia and veneering porcelain. Veneering with a thin layer of porcelain powder as the bond coating has no obvious effect on the bonding strength. Sandblasting and veneering with a thin layer of porcelain powder as a bond coating can significantly improve the bonding strength between zirconia and veneering porcelain.