Related Experiment Video

Updated: Oct 13, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line

T Tokunaga1, T Tsuchida, H Kijima

  • 1Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan.

British Journal of Cancer
|August 23, 2000
PubMed

Insights

Hammerhead ribozymes targeting mutated K-ras (codon 12) effectively inhibited colon cancer cell growth and tumor development. This approach suppressed vascular endothelial growth factor and promoted thrombospondin, inducing apoptosis and reducing tumor size.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Therapy

Background:

  • K-ras oncogene mutations are critical in colon cancer progression.
  • Targeting mutant K-ras offers a potential therapeutic strategy for colon cancer.

Purpose of the Study:

  • To investigate the efficacy of a hammerhead ribozyme (KrasRz) in inactivating mutant K-ras in colon cancer cells.
  • To evaluate the effects of KrasRz on colon cancer cell growth, angiogenesis, and apoptosis.

Main Methods:

  • A hammerhead ribozyme targeting codon 12 mutated K-ras mRNA was designed.
  • The ribozyme (pHbeta/KrasRz) was introduced into SW480 colon cancer cells.
  • In vitro cleavage assays, cell culture growth studies, xenotransplantation in nude mice, and gene expression analysis were performed.

Main Results:

  • KrasRz specifically cleaved mutant K-ras mRNA in vitro.
  • SW480/KrasRz cells exhibited reduced growth rates and decreased xenotransplantability.
  • Tumor volume in xenografts was significantly smaller, with suppressed VEGF and enhanced TSP1 expression.
  • Apoptosis-related features were observed in SW480/KrasRz cells.

Conclusions:

  • Hammerhead ribozyme-mediated inactivation of mutant K-ras mRNA is a promising strategy for colon cancer therapy.
  • This approach leads to growth suppression, apoptosis induction, and modulation of angiogenic factors.
  • Targeting K-ras mutations with ribozymes offers a potential pathway for colon cancer treatment.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...