Related Experiment Video

Updated: Jan 21, 2026

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
08:55

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats

Published on: April 15, 2016

9.9K

PMPCB Silencing Sensitizes HCC Tumor Cells to Sorafenib Therapy

Jian-Feng Zheng1, Shaozhong He2, Zongyue Zeng3

  • 1Department of Laboratory Medicine, Baoan Central Hospital of Shenzhen, The Fifth Affiliated Hospital of Shenzhen University, Shenzhen 518102, Guangdong, P.R. China.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|July 25, 2019
PubMed

Insights

Targeting mitochondrial-processing peptidase beta subunit (PMPCB) can overcome sorafenib resistance in hepatocellular carcinoma (HCC). Silencing PMPCB or MCL-1 enhances sorafenib efficacy, improving survival outcomes for HCC patients.

Area of Science:

  • Hepatocellular carcinoma (HCC) research
  • Cancer therapy resistance mechanisms
  • Molecular oncology

Background:

  • Hepatocellular carcinoma (HCC) frequently develops resistance to targeted therapies like sorafenib, leading to treatment failure.
  • Mitochondrial-processing peptidase (PMPC) has been identified as a key contributor to sorafenib resistance in HCC.
  • The specific role of the PMPC beta subunit (PMPCB) in this resistance mechanism requires further investigation.

Purpose of the Study:

  • To investigate the role of PMPCB in sorafenib resistance in hepatocellular carcinoma (HCC).
  • To evaluate the therapeutic potential of targeting PMPCB in combination with sorafenib for HCC treatment.
  • To elucidate the molecular mechanisms underlying PMPCB-mediated sorafenib resistance.

Main Methods:

  • Utilized short hairpin RNA (shRNA) to silence PMPCB in HCC cell lines and tumor-bearing mice.
  • Assessed tumor cell susceptibility to sorafenib, liver tumor burden, and animal survival.
  • Investigated the impact of PMPCB silencing on PINK1-Parkin signaling and MCL-1 expression.
  • Correlated pre-treatment MCL-1 expression with survival outcomes in HCC patients.

Main Results:

  • Silencing PMPCB significantly increased HCC cell sensitivity to sorafenib, reduced tumor burden, and improved survival in mice.
  • Combination therapy with sorafenib and PMPCB shRNA attenuated tumor growth and enhanced survival.
  • PMPCB knockdown promoted apoptosis by activating PINK1-Parkin signaling and downregulating MCL-1.
  • Higher pre-treatment MCL-1 levels correlated with poorer survival in sorafenib-treated HCC patients.

Conclusions:

  • PMPCB plays a crucial role in mediating sorafenib resistance in hepatocellular carcinoma.
  • Targeting PMPCB, potentially through knockdown strategies, offers a promising approach to overcome sorafenib resistance.
  • Combination therapy involving sorafenib with PMPCB or MCL-1 knockdown presents a viable strategy to improve treatment outcomes for advanced HCC patients.
Keywords:
HCCMCL-1MPPBPINK1PMPCBParkinbeta-MPPhepatocellular carcinomasorafenib

More Related Videos

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma08:00

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

Published on: April 16, 2019

19.2K
Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.6K

Related Concept Videos

Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.4K
Stem Cell Therapy for Tissue Regeneration01:21

Stem Cell Therapy for Tissue Regeneration

Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
4.6K
Group Therapy01:26

Group Therapy

Group therapy is a sociocultural approach to psychological treatment, where individuals with shared psychological challenges come together under the guidance of a mental health professional. This therapeutic modality offers unique opportunities for individuals to connect, share, and grow within the context of a supportive group. By fostering mutual understanding and collaboration, group therapy can address a range of psychological concerns effectively, often complementing or surpassing the...
375
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.9K
Psychodynamic Therapy01:29

Psychodynamic Therapy

Psychodynamic therapies emphasize the exploration of unconscious processes and early childhood experiences as fundamental contributors to psychological difficulties. These therapies, deeply rooted in Freud's psychoanalytic theory, aim to uncover and resolve unconscious conflicts, granting individuals insights that promote emotional and behavioral healing. Contemporary psychodynamic approaches have evolved, integrating a broader range of influences and methodologies while still valuing the...
525
Humanistic Therapy01:24

Humanistic Therapy

Humanistic therapies emphasize personal growth, self-understanding, and the fulfillment of human potential. Rooted in the belief that individuals inherently strive toward self-actualization, these approaches encourage clients to explore their feelings and experiences in a supportive, nonjudgmental environment. Humanistic therapies differ from psychodynamic approaches by focusing on conscious experiences, present circumstances, and the potential for self-improvement rather than past conflicts...
339