Mitochondrial Dynamics Mediated by DRP1 and MFN2 Contributes to Cisplatin Chemoresistance in Human Ovarian Cancer SKOV3 cells DOI Creative Commons

Guang-Ping Zou,

Chunxia Yu,

Sheng-Lan Shi

et al.

Journal of Cancer, Journal Year: 2021, Volume and Issue: 12(24), P. 7358 - 7373

Published: Jan. 1, 2021

Cisplatin (DDP) is the first-line chemotherapeutic agent for ovarian cancer. However, development of DDP resistance seriously influences effect and prognosis It was reported that can directly impinge on mitochondria activate intrinsic apoptotic pathway. Herein, role mitochondrial dynamics in chemoresistance human cancer SKOV3 cells investigated. In DDP-resistant SKOV3/DDP cells, fission protein DRP1 down-regulated, while fusion MFN2 up-regulated. accordance with expression MFN2, average length significantly increased cells. DDP-sensitive parental downregulation upregulation proteins including MFN1,2 OPA1 occurred at day 2~6 under cisplatin stress. Knockdown or overexpression promoted to cisplatin. Intriguingly, weaker migration capability lower ATP level were detected Respective knockdown using siRNA efficiently reversed dynamics, level. Moreover, aggravated DDP-induced ROS production, membrane potential disruption, pro-apoptotic BAX Cleaved Caspase-3/9 contrast, alleviated Thus, these results indicate mediated by contributes will also provide a new strategy prevent targeting dynamics.

Language: Английский

Targeting LRP6: A new strategy for cancer therapy DOI Creative Commons
Wei Xue, Bo Zhu, Kaili Zhao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107200 - 107200

Published: May 6, 2024

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), vital component Wnt signaling pathway, has emerged as an intriguing candidate. As cell-surface receptor and co-receptor, LRP6 frequently overexpressed various types, implicating its pivotal role driving progression. The pursuit target for treatment gained substantial traction, offering promising avenue therapeutic intervention. Here, this comprehensive review explores recent breakthroughs our understanding LRP6's functions underlying mechanisms, providing profound discussion involvement pathogenesis drug resistance. Importantly, we go beyond discussing by diverse potential approaches targeting enigmatic protein. These encompass wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, peptides that modulate expression or disrupt interactions. In addition, also discussed challenges associated with developing inhibitors their advantages over inhibitors, well drugs have entered phase II clinical trials. By shedding light on innovative strategies, aim to underscore significance valuable multifaceted treatment, igniting enthusiasm further research facilitating translation into applications.

Language: Английский

Citations

10
Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers DOI Creative Commons
Nooshafarin Shirani,

N. Abdi,

Matin Chehelgerdi

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 24, 2025

Exosomes, as key mediators of intercellular communication, have been increasingly recognized for their role in the oncogenic processes, particularly facilitating drug resistance. This article delves into emerging evidence linking exosomal lncRNAs to modulation resistance mechanisms cancers such ovarian, cervical, and endometrial cancer. It synthesizes current research findings on how these influence cancer cell survival, tumor microenvironment, chemotherapy efficacy. Additionally, review highlights potential therapeutic strategies targeting lncRNAs, proposing a new frontier overcoming By mapping interface resistance, this aims provide comprehensive understanding that could pave way innovative treatments improved patient outcomes female reproductive system cancers.

Language: Английский

Citations

1
Platinum Derivatives Effects on Anticancer Immune Response DOI Creative Commons
Cédric Rébé,

Lucie Demontoux,

Thomas Pilot

et al.

Biomolecules, Journal Year: 2019, Volume and Issue: 10(1), P. 13 - 13

Published: Dec. 20, 2019

Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition their direct cytotoxic effects, these also impact host immune system, which might enhance or counteract antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin oxaliplatin, belongs chemotherapeutical used numerous types. Here, we will focus on effects molecules response. These can induce not immunogenic cell death (ICD), some strategies have been found further it. They regulate cells’ fate. Platinum derivatives lead activation. Additionally, they dampen cells by selective killing inhibiting activity, particularly modulating checkpoints’ expression.

Language: Английский

Citations

66
PBK, targeted by EVI1, promotes metastasis and confers cisplatin resistance through inducing autophagy in high-grade serous ovarian carcinoma DOI Creative Commons

Hanlin Ma,

Yingwei Li, Xiangxiang Wang

et al.

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(3)

Published: Feb. 18, 2019

Abstract High-grade serous ovarian carcinoma (HGSOC) is the most lethal type of gynecologic malignancy. Chemoresistance main reason for poor prognosis HGSOC. PDZ-binding kinase (PBK) promotes malignant progression various carcinomas. However, roles and clinical significance PBK in HGSOC remain unclear. Here, we reported that was overexpressed tissues cell lines. High expression associated with a prognosis, metastasis, cisplatin resistance Overexpression promoted autophagy enhanced via ERK/mTOR signaling pathway. Further study showed inhibition by chloroquine or bafilomycin A1 reversed PBK-induced resistance. decreased cancer responsiveness to treatment through inducing vivo. We also demonstrated inhibitor OTS514 augmented growth effect vitro Moreover, ecotropic viral integration site-1 (EVI1) could regulate directly targeting promoter region. In conclusion, high correlated promoting might be promising target early diagnosis individual cancer.

Language: Английский

Citations

59
Drug resistance evaluation in novel 3D in vitro model DOI Open Access
Marta Nowacka, Karolina Sterzyńska, Małgorzata Andrzejewska

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 138, P. 111536 - 111536

Published: March 31, 2021

Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high is development of drug resistance. It can be related to changes in expression many resistance genes as well extracellular matrix proteins and cell density tumor. We developed a simple two-dimensional three-dimensional model sensitive A2780 resistant cisplatin paclitaxel variants ovarian line. Using MTT assay, we compared culture conditions. Real-time polymerase chain reaction analysis was used compare genes. spheroids determined by immunohistochemistry. observed moderate increase significant between Our findings show that may play crucial role cells traditional culture. On other hand, result from different mechanisms such spheroid, capacity diffuse into spheroid.

Language: Английский

Citations

55
The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers cisplatin resistance in ovarian cancer DOI Creative Commons
Liangliang Ren,

Xingrong Qing,

Jihong Wei

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 26, 2023

Sustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure cancer. However, the mechanism underlying DDR sustaining cancer cells remains unclear. In current study, we found that expression DDUP microprotein, encoded by CTBP1-DT lncRNA, drastically increased cisplatin-resistant ovarian and was inversely correlated cisplatin-based therapy response. Using a patient-derived human cell model, observed damage-induced foci sustained RAD18/RAD51C RAD18/PCNA complexes at sites damage, consequently resulting cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) proliferating nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted DDUP/RAD18 interaction abolished effect on prolonged signaling, which resulted hypersensitivity vivo. Altogether, our study provides insights into DDUP-mediated aberrant describes potential novel therapeutic approach for management platinum-resistant

Language: Английский

Citations

21
The impact of varying levels of residual disease following cytoreductive surgery on survival outcomes in patients with ovarian cancer: a meta-analysis DOI Creative Commons
Dana M. Chase, Anadi Mahajan, David A. Scott

et al.

BMC Women s Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 15, 2024

Abstract Background Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated poorer survival outcomes compared no residual disease. We performed a meta-analysis to assess the impact of varying levels status on who have undergone primary or interval setting new therapies for this Methods Medline, Embase, and Cochrane databases (January 2011 – July 2020) grey literature, bibliographic key conference proceedings, were searched eligible studies. Fixed random-effects meta-analyses progression by level across Heterogeneity between comparisons was explored via type surgery, stage, adjuvant chemotherapy. Results Of 2832 database 16 supplementary search articles screened, 50 studies selected; most observational The showed that median progression-free overall decreased progressively increasing (residual categories 0 cm, > 0–1 cm 1 cm). Compared disease, hazard ratios (HR) increased category (1.75 [95% confidence interval: 1.42, 2.16] 2.14 [1.34, 3.39] cm), also reduced (HR versus 1.75 [ 1.62, 1.90] 2.32 [1.97, 2.72] All significant ( p < 0.05). Subgroup analyses an association progression/reduced irrespective Conclusions This provided update demonstrated still highly predictive adults despite changes therapy over last decade. Higher numerical than lower categories.

Language: Английский

Citations

6
A novel TCGA-validated programmed cell-death-related signature of ovarian cancer DOI Creative Commons
Xintong Cai,

Jie Lin,

Liu L

et al.

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 23, 2024

Ovarian cancer (OC) is a gynecological malignancy tumor with high recurrence and mortality rates. Programmed cell death (PCD) an essential regulator in metabolism, whose functions are still unknown OC. Therefore, it vital to determine the prognostic value therapy response of PCD-related genes

Language: Английский

Citations

6
Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer DOI Creative Commons
Ying Liu, Xiang Ao,

Guoqiang Ji

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Nov. 29, 2021

Gastric cancer (GC) is one of the most common malignant tumors digestive systems worldwide, with high recurrence and mortality. Chemotherapy still standard treatment option for GC can effectively improve survival life quality patients. However, emergence drug resistance, clinical application chemotherapeutic agents has been seriously restricted in Although mechanisms resistance have broadly investigated, they are largely unknown. MicroRNAs (miRNAs) a large group small non-coding RNAs (ncRNAs) widely involved occurrence progression many types, including GC. An increasing amount evidence suggests that miRNAs may play crucial roles development by regulating some resistance-related proteins as well gene expression. Some also exhibit great potential novel biomarkers predicting response to chemotherapy therapeutic targets In this review, we systematically summarize recent advances focus on their molecular progression. We highlight

Language: Английский

Citations

33
Downregulating vaccinia-related kinase 1 by luteolin suppresses ovarian cancer cell proliferation by activating the p53 signaling pathway DOI Creative Commons

Xuboya Chang,

Satoshi Tamauchi, Kosuke Yoshida

et al.

Gynecologic Oncology, Journal Year: 2023, Volume and Issue: 173, P. 31 - 40

Published: April 17, 2023

Language: Английский

Citations

16