Plk3 Enhances Cisplatin Sensitivity of Nonsmall-Cell Lung Cancer Cells through Inhibition of the PI3K/AKT Pathway via Stabilizing PTEN DOI Creative Commons

Mengshan Xu,

Xiaoyun Deng,

Nana Xiang

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(8), P. 8995 - 9002

Published: Feb. 12, 2024

Polo-like kinase 3 (Plk3) is involved in tumor development with a suppressive function. However, the effect of Plk3 on chemoresistance remains unclear. It has been documented that activation PI3K/AKT signaling pathway by PTEN loss significantly enhances nonsmall-cell lung cancer (NSCLC). This study aims to evaluate regulation and identify targets underlying mechanisms could be used relieve chemoresistance. Our results showed silencing reduced expression activated dephosphorylating destabilizing NSCLC cells. Reducing promoted drug resistance cisplatin (DDP), while overexpressing DDP sensitivity. these effects were attenuated when MK2206, inhibitor, was applied. In conclusion, upregulation sensitized cells toward DDP, which provides potential target restore chemoresponse. We provided novel evidence PTEN/PI3K/AKT regulated through phosphorylation highlighted critical role NSCLC.

Language: Английский

Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review) DOI Creative Commons

Yichen Tian,

Yongrong Lei,

Yani Wang

et al.

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 63(5)

Published: Aug. 28, 2023

Multidrug resistance (MDR) seriously limits the clinical application of chemotherapy. A mechanism underlying MDR is overexpression efflux transporters associated with chemotherapeutic drugs. P‑glycoprotein (P‑gp) an ATP‑binding cassette (ABC) transporter, which promotes by pumping out drugs and reducing their intracellular concentration. To date, P‑gp has been detected in various types chemoresistant cancer inhibiting P‑gp‑related suggested. The present review summarizes mechanisms mediated different tumors evaluated related signaling pathways, aim improving understanding current status P‑gp‑mediated resistance. This focuses on main MDR, providing a reference for study reversing MDR. first involves decreasing activity altering its conformation or hindering P‑gp‑chemotherapeutic drug binding. second inhibitory expression to reduce efflux. third knocking ABCB1 gene. Potential strategies that can inhibit include certain natural products, synthetic compounds biological techniques. It important screen lead candidate techniques inhibition, identify inhibitors targeting relevant pathways overcome

Language: Английский

Citations

54
Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers DOI Creative Commons
Lei Zhang, Biwei Ye, Zhuo Chen

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(3), P. 982 - 997

Published: Oct. 7, 2022

Chemotherapy is one of the important methods to treat cancer, and emergence multidrug resistance (MDR) major cause for failure cancer chemotherapy. Almost all anti-tumor drugs develop drug over a period time application in patients, reducing their effects on killing cells. Chemoresistance can lead rapid recurrence cancers ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with complex process genes, factors, pathways, steps, today MDR-associated mechanisms largely unknown. In this paper, from aspects protein–protein interactions, alternative splicing (AS) pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance cell functions, influence tumor microenvironment, we summarize molecular cancers. end, prospects exploration antitumor that reverse briefly discussed angle systems improved targeting properties, biocompatibility, availability, other advantages.

Language: Английский

Citations

56
Current Status and Prospects of Targeted Therapy for Osteosarcoma DOI Creative Commons
Zunguo Hu,

Shuang Wen,

Zijun Huo

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(21), P. 3507 - 3507

Published: Nov. 5, 2022

Osteosarcoma (OS) is a highly malignant tumor occurring in bone tissue with high propensity to metastasize, and its underlying mechanisms remain largely elusive. The OS prognosis poor, improving the survival of patients remains challenge. Current treatment methods such as surgical approaches, chemotherapeutic drugs, immunotherapeutic drugs ineffective. As research progresses, targeted therapy gradually becoming irreplaceable. In this review, several modalities for osteosarcoma, surgery, chemotherapy, immunotherapy, are briefly described, followed by discussion therapy, important targets, new technologies osteosarcoma treatment.

Language: Английский

Citations

55
Current Status and Prospects of Clinical Treatment of Osteosarcoma DOI Creative Commons
Zong-Yuan Jiang, Ji‐Bin Liu, Xiaofeng Wang

et al.

Technology in Cancer Research & Treatment, Journal Year: 2022, Volume and Issue: 21

Published: Jan. 1, 2022

Osteosarcoma, one of the common malignant tumors in skeletal system, originates mesenchymal tissue, and most susceptible area occurrence is metaphysis with its abundant blood supply. Tumors are characterized by highly spindle stromal cells that can produce bone-like tissue. Most osteosarcoma primary, a few secondary. Osteosarcoma occurs primarily children adolescents undergoing vigorous bone growth development. cases involve rapid tumor development early metastasis. In recent years, research has grown areas molecular biology, imaging medicine, biological materials, applied anatomy, surgical techniques, biomechanics, comprehensive treatment tumors. With developments biology tissue bioengineering, methods have also made great progress, especially limb salvage treatment, which significantly enhances quality life after surgery improves 5-year survival rate patients This article provides review salvage, immunotherapy, gene therapy, targeted therapy from traditional amputation to neoadjuvant chemotherapy, providing reference for current clinical treatments osteosarcoma.

Language: Английский

Citations

44
Natural products reverse cancer multidrug resistance DOI Creative Commons
Jiayu Zou, Qilei Chen,

Xiao-Ci Luo

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 8, 2024

Cancer stands as a prominent global cause of death. One the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse MDR. Discovering novel potential modulators to reduce MDR by has become popular research area across globe. Numerous mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their modulatory activity. regulating signaling pathways or relevant expressed protein gene. Here we perform deep review previous achievements, advances in development treatment This aims provide some insights study products.

Language: Английский

Citations

14
The prevention of multi-drug resistance in cancers through the application of nanotechnology-based targeted delivery systems for combination therapies involving traditional Chinese medicine DOI Creative Commons
Salik Abdullah,

Shreya Mukherjee,

Shweta Shweta

et al.

Pharmacological Research - Modern Chinese Medicine, Journal Year: 2024, Volume and Issue: 10, P. 100386 - 100386

Published: Feb. 4, 2024

The most significant obstacle in addressing cancer is the development of multidrug resistance during chemotherapy. Cancer cells have ability to endure numerous cycles traditional chemotherapy drugs before ultimately developing treatment. Combining a strategy used address problem resistance. Persistent challenges with synthetic include catastrophic adverse reactions and other consequences. Natural compounds originating from Chinese medicine are acknowledged for their minimal toxicity possible benefits reversing induced by mainstream chemotherapeutic or targeted treatments. (MDR) an immediate clinical justification unsatisfactory recurrence metastasis precipitated MDR, leading high risk death. unique nano-delivery method therapeutic management MDR cancers has emerged as key use nanotechnology. Because its anticancer prospective, (TCM)-combination therapy emerging treatment modality essential option cancer. By precisely regulating release medicines delivering pharmaceuticals cancerous cells, nano drug-delivery devices offer amazing pave way growth TCM-combination therapies. present review examines literature on three important topics: mechanism chemotherapy, role herbs formulation treatment, incorporation TCM nanotechnology-based drug delivery systems circumvent limitations system. Major sources work PubMed, Google Scholar, ResearchGate, Embase, ScienceDirect. All aspects pertaining TCM, nanotechnology more than 50 years were considered, emphasis formulation, various forms advances system result nanotechnology, everything else between. As becomes closely associated realm practice broadening. Furthermore, it enhances prospects future research facilitates advancement modern Traditional Medicine (TCM). integrating into meticulously designed system, will enhance both treat prevent diseases even greater efficacy previously. This article nano-TCM explores characteristics, compositions, relevant techniques preparation application MDR. In addition, comprehensive elucidation had been given respect objective this study was analyze existing body (TCM) that can be encompasses like active components utilization (MDR), potential advancements obstacles TCM-based combinations.

Language: Английский

Citations

13
Tumor microenvironment diversity and plasticity in cancer multidrug resistance DOI
Zhi Li, Peihao Yin

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188997 - 188997

Published: Oct. 12, 2023

Language: Английский

Citations

17
Alkaliptosis induction counteracts paclitaxel‐resistant ovarian cancer cells via ATP6V0D1‐mediated ABCB1 inhibition DOI
Fangquan Chen, Junhao Lin, Rui Kang

et al.

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(8), P. 1515 - 1527

Published: May 15, 2024

Abstract Paclitaxel serves as the cornerstone chemotherapy for ovarian cancer, yet its prolonged administration frequently culminates in drug resistance, presenting a substantial challenge. Here we reported that inducing alkaliptosis, rather than apoptosis or ferroptosis, effectively overcomes paclitaxel resistance. Mechanistically, ATPase H + transporting V0 subunit D1 (ATP6V0D1), key regulator of plays pivotal role by mediating downregulation ATP‐binding cassette subfamily B member 1 (ABCB1), multidrug resistance protein. Both ATP6V0D1 overexpression through gene transfection and pharmacological enhancement protein stability using JTC801 inhibit ABCB1 upregulation, resulting growth inhibition drug‐resistant cells. Additionally, increasing intracellular pH to alkaline (pH 8.5) via sodium hydroxide application suppresses expression, whereas reducing acidic conditions 6.5) with hydrochloric acid amplifies expression Collectively, these results indicate potentially effective therapeutic strategy targeting paclitaxel‐resistant cancer ATP6V0D1‐dependent alkaliptosis.

Language: Английский

Citations

8
Novel insight into mitochondrial dynamin-related protein-1 as a new chemo-sensitizing target in resistant cancer cells DOI
Samar Sami Alkafaas,

Omar K. Obeid,

Mustafa Ali Radwan

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 150, P. 107574 - 107574

Published: June 22, 2024

Language: Английский

Citations

5
Supramolecular host-guest nanosystems for overcoming cancer drug resistance DOI Open Access

Sha Wu,

Miaomiao Yan,

Minghao Liang

et al.

Cancer Drug Resistance, Journal Year: 2023, Volume and Issue: 6(4), P. 805 - 27

Published: Nov. 22, 2023

Cancer drug resistance has become one of the main challenges for failure chemotherapy, greatly limiting selection and use anticancer drugs dashing hopes cancer patients. The emergence supramolecular host-guest nanosystems brought field chemistry into nanoworld, providing a potential solution to this challenge. Compared with conventional chemotherapeutic platforms, can reverse by increasing uptake, reducing efflux, activating drugs, inhibiting DNA repair. Herein, we summarize research progress overcoming discuss future direction in field. It is hoped that review will provide more positive references promoting development nanosystems.

Language: Английский

Citations

12