Ribociclib Inhibits P-gp-Mediated Multidrug Resistance in Human Epidermoid Carcinoma Cells DOI Creative Commons
Lei Zhang,

Biwei Ye,

Yunfeng Lin

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cells. In this study, we determined the effect CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR human epidermoid carcinoma cell line, KB-C2, which is widely used for studying P-gp-mediated cancers. incubation KB-C2 cells with (3-9 µM) increased colchicine, a substrate P-gp. expression P-gp was down-regulated at both translation and transcription levels. Furthermore, produced 3.5-fold increase basal activity ATPase, concentration required to 50% (EC50) 0.04 μM. Docking studies indicated that interacted drug-substrate binding site short-term long-term intracellular accumulation doxorubicin greatly co-cultured ribociclib, indicating inhibited drug efflux results our study indicate LEE011 may potential agent combined therapy cancers mediated MDR.

Language: Английский

CDK4/6 Inhibitor Resistance in Hormone Receptor-Positive Metastatic Breast Cancer: Translational Research, clinical trials, and Future Directions DOI Open Access
Jin Sun Lee,

Hannah Hackbart,

Xiaojiang Cui

et al.

Published: June 28, 2023

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms both progression-free survival overall survival. However, resistance to inhibitors remains a challenge, limiting their long-term efficacy. Understanding complex mechanisms driving is crucial development novel therapeutic strategies improvement patient outcomes. Translational research efforts, preclinical models biomarker studies, offer valuable insight into may guide identification combination therapies. This review paper aims outline reported underlying inhibitor resistance, drawing insights from data translational order help direct future receptor positive metastatic

Language: Английский

Citations

7
Functionalized nanoparticles crossing the brain–blood barrier to target glioma cells DOI Creative Commons

Yongyan Wu,

Yufeng Qian, Wei Peng

et al.

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15571 - e15571

Published: July 4, 2023

Glioma is the most common tumor of central nervous system (CNS), with a 5-year survival rate <35%. Drug therapy, such as chemotherapeutic and immunotherapeutic agents, remains one main treatment modalities for glioma, including temozolomide, doxorubicin, bortezomib, cabazitaxel, dihydroartemisinin, immune checkpoint inhibitors, well other approaches siRNA, ferroptosis induction, etc . However, filter function blood-brain barrier (BBB) reduces amount drugs needed to effectively target CNS tumors, making it reasons poor drug efficacies in glioma. Thus, finding suitable delivery platform that can cross BBB, increase aggregation retainment tumoral areas avoid accumulation non-targeted an unsolved challenge glioma therapy. An ideal therapy should have following features: (1) prolonged life circulation effective penetration through BBB; (2) adequate within (3) controlled-drug release modulation; (4) good clearance from body without significant toxicity immunogenicity, etc. In this regard, due their unique structural features, nanocarriers span BBB cells surface functionalization, providing new strategy delivery. article, we discuss characteristics pathways different crossing targeting by listing materials platforms, lipid materials, polymers, nanocrystals, inorganic nanomaterials,

Language: Английский

Citations

7
Development of an efficient liposomal DOX delivery formulation for HCC therapy by targeting CK2α DOI
Ruixia Zhao, Sinan Cheng, Xue Bai

et al.

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(4)

Published: April 1, 2024

Hepatocellular carcinoma (HCC) is a digestive tract cancer with high mortality and poor prognosis, especially in China. Current chemotherapeutic drugs lead to low efficacy, side effects due weak targeting specificity rapidly formed multidrug resistance (MDR). Based on the previous studies doxorubicin (DOX) formulation for therapy, we developed novel DOX delivery chemotherapy of HCC resistant HCC. HCSP4 was previously screened casein kinase 2α (CK2α) predicted as its specific target cells our lab. In study, miR125a-5p firstly an MDR inhibiting miRNA, then CK2α validated using CK2α-/-HepG2 cells. above, liposomal formulation, HCSP4/Lipo-DOX/miR125a-5p synthesized tested therapeutic efficacy vitro. The results showed that targeted specifically sensitively, presented satisfied HCC, particularly potential mechanism explored, inhibited expression MDR-relevant genes including ATP-binding cassette subfamily B member 1 (ABCB1, also known P-glycoprotein), C 5 (ABCC5), enhancer zeste homolog 2 (EZH2), ATPase Na

Language: Английский

Citations

2
Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors DOI Creative Commons
Xu Zhang, Yuxiang Wang, Xi Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 12, 2023

Abstract Phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma (ESCC). It is great importance to identify potential biomarkers predict or monitor efficacy PI3Kα in an aim improve clinical responsive rate ESCC. Here, ESCC PDXs with CCND1 amplification were found be more sensitive CYH33, a novel PI3Kα-selective inhibitor trials treatment advanced solid tumors including Elevated level cyclin D1, p21 and Rb was CYH33-sensitive cells compared those resistant cells. CYH33 significantly arrested but not at G1 phase, which associated accumulation suppression phosphorylation by CDK4/6 CDK2. Hypo-phosphorylation attenuated transcriptional activation SKP2 E2F1, turn hindered SKP2-mediated degradation reinforced p21. Moreover, sensitized CYH33. These findings provided mechanistic rationale evaluate patients harboring amplified combined regimen proficient Rb.

Language: Английский

Citations

4
Ribociclib Inhibits P-gp-Mediated Multidrug Resistance in Human Epidermoid Carcinoma Cells DOI Creative Commons
Lei Zhang,

Biwei Ye,

Yunfeng Lin

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cells. In this study, we determined the effect CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR human epidermoid carcinoma cell line, KB-C2, which is widely used for studying P-gp-mediated cancers. incubation KB-C2 cells with (3-9 µM) increased colchicine, a substrate P-gp. expression P-gp was down-regulated at both translation and transcription levels. Furthermore, produced 3.5-fold increase basal activity ATPase, concentration required to 50% (EC50) 0.04 μM. Docking studies indicated that interacted drug-substrate binding site short-term long-term intracellular accumulation doxorubicin greatly co-cultured ribociclib, indicating inhibited drug efflux results our study indicate LEE011 may potential agent combined therapy cancers mediated MDR.

Language: Английский

Citations

7