Interfering RNA screening finds the key to drug therapy for breast cancer resistance

Recently, researchers at Vanderbilt University in the United States published a new research progress in the international academic journal Cancer Research. They used full-kinome siRNA to discover the mechanism of estrogen receptor-positive breast cancer cells against CDK4/6 inhibitors. Screening to find kinases that increase the sensitivity of cells to ribociclib after down-regulation.

In the screening results, the researchers found that the down-regulation of PDK1 kinase expression can increase the sensitivity of ER-positive MCF-7 cells to ribociclib. Drug inhibition of PDK1 using GSK2334470, a combination of ribociclib or palbociclib (another CDK inhibitor) synergistically inhibits proliferation and promotes apoptosis in a range of ER-positive breast cancer cell lines.

The researchers also screened MCF-7, T47D and HCC1428 cells against ribociclib after chronic drug exposure, and found that these intracellular PDK1, P-RSK2, P-AKT were compared to drug-sensitive cells. Both the P-S6 and the P-S6 will increase.

Cell cycle analysis showed that inhibition of CDK4/6 could not induce G1 arrest, S phase reduction and cell senescence in cells resistant to ribociclib. Cells with drug resistance showed a significant increase in P-CDK2, cyclin A, cyclin D, cyclin E, and S477/T479 P-AKT, a CDK2-dependent phosphorylation site on AKT, phosphorylated The S phase, which is limited to the cell cycle, is important for AKT to exert full kinase activity.

The researchers also found that GSK2334470 or the CDK inhibitor dinaciclib regains drug sensitivity to CDK4/6 inhibitors in cells that are resistant to ribociclib; however, the drug combination of ribociclib/GSK2334470 inhibits drug-resistant cells. More powerful than ribociclib/dinaciclib. Ribociclib/ GSK233447 completely abolished the expression of P-Rb, P-S6, P-RSK2, P-CDK2, cyclin A, cyclin D1 and cyclin E, but ribociclib/dinaciclib could not be achieved.

Further studies have shown that ribociclib in combination with GSK233447 or the PI3Kα inhibitor alpelisib is capable of inducing tumor regression in a mouse model of MCF-7 xenografting. Finally, the researchers also found that after short-term treatment with palbociclib, ER-positive tumors showed an increase in the expression levels of PDK1, P-S6 and cyclin D1. These data indicate that PI3K/PDK1 plays an important role in mediating tumor cell resistance to CDK4/6 inhibitors.

Shanghai Chuangsai Technology has excellent performance, interleukin cytokines, fetal bovine serum, electrophoresis equipment scientific instruments, raw material drug standards, chemical reagents, cell culture consumables, Shanghai Chuangsai, mass products special promotions, welcome to inquire!

Hair Thinning Scissors

Hair Thinning Scissors,Hairdressing Thinning Scissors,W-Teeth Hair Thinning Scissors,440C Stainless Steel Hair Scissors

Zhangjiagang Mister Tools Co., Ltd , https://www.mingshitools.com