Lysosome-associated protein transmembrane4β is involved in multidrug resistance processes of colorectal cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
• Drug resistance, particularly to oxaliplatin (OXA), is a significant challenge in CRC treatment.
• Understanding the mechanisms of drug resistance is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the drug resistance mechanism in an oxaliplatin-resistant colorectal cancer cell line (HT-29/L-OHP).
• To examine the expression of lysosome-associated protein transmembrane 4β (LAPTM4β), a gene associated with drug resistance.
• To evaluate the potential of LAPTM4β as a biomarker for colorectal cancer drug resistance.

Main Methods:

• Establishment of an oxaliplatin-resistant HT-29 cell line (HT-29/L-OHP) using a drug concentration gradient method.
• Analysis of cell apoptosis via flow cytometry.
• Quantification of LAPTM4β mRNA expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
• Assessment of LAPTM4β-35 protein expression through western blot analysis.
• Microscopic examination of cell morphology.

Main Results:

• The HT-29/L-OHP cells exhibited altered morphology with increased intercellular space and scattered growth compared to HT-29 cells.
• Apoptotic rates were significantly lower in HT-29/L-OHP cells (11.7%) than in HT-29 cells (17.7%) (P<0.05).
• Both LAPTM4β mRNA and LAPTM4β-35 protein expression levels were significantly elevated in the HT-29/L-OHP cells compared to HT-29 cells (P<0.05).

Conclusions:

• Lysosome-associated protein transmembrane 4β (LAPTM4β) expression is significantly upregulated in oxaliplatin-resistant colorectal cancer cells.
• LAPTM4β may play a role in the multidrug resistance mechanisms observed in colorectal cancer.
• LAPTM4β holds potential as a novel biomarker for predicting or monitoring drug resistance in colorectal cancer.