Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells

Abstract

Objective: Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated.

Methods: In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay. Dose response curve analysis was performed in AGS and MKN-45 cells with stable ASNS knockdown to assess sensitivity to cisplatin. Xenograft experiment was performed to examine in vivo synergistic effects of ASNS depletion and cisplatin on tumor growth. Expression level of ASNS was evaluated in human patient samples using quantitative PCR. Kaplan–Meier curve analysis was performed to evaluate association between ASNS expression and patient survival.

Results: Transient knockdown of ASNS inhibited cell proliferation and colony formation in AGS and MKN-45 cells. Stable knockdown of ASNS conferred sensitivity to cisplatin in these cells. Depletion of ASNS and cisplatin treatment exerted synergistic effects on tumor growth in AGS xenografts. Moreover, ASNS was found to be up-regulated in human gastric cancer tissues compared with matched normal colon tissues. Low expression of ASNS was significantly associated with better survival in gastric cancer patients.

Conclusion: ASNS may contribute to gastric cancer tumorigenesis and may represent a novel therapeutic target for prevention or intervention of gastric cancer.

Keywords:

• Asparagine synthetase
• chemo-sensitivity
• gastric cancer
• tumor progression

Disclosure statement

The authors declare that they have no conflicts of interest to disclose.

Funding information

This work was supported by a grant from the National Nature Science Foundation of China (Grant Number: 81070283).