Open Access

Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells

  • Authors:
    • Wenjing Zhang
    • Cui Wang
    • Xiaomei Hu
    • Yanzhen Lian
    • Caili Ding
    • Liang Ming
  • View Affiliations

  • Published online on: February 18, 2022     https://doi.org/10.3892/or.2022.8288
  • Article Number: 77
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Warburg effect or aerobic glycolysis is a hallmark of cancer. Lactate dehydrogenase (LDH), which catalyzes conversion of pyruvate into lactate, serves a critical role during Warburg effect. LDH A chain (LDHA), a member of the LDH family, is upregulated in multiple types of cancer and serves a vital role in tumor growth and progression. However, its expression and function in cervical cancer has not been characterized. The present study evaluated LDHA expression in The Cancer Genome Atlas database and found that LDHA was upregulated in cervical cancer compared with normal tissue. To clarify the role of LDHA in cervical cancer HeLa and SiHa cells, lentiviral shRNA was used to stably knockdown LDHA and oxamate, a small‑molecule inhibitor of LDHA, was used to inhibit the activity of LDHA. Glucose uptake assay, lactate production measurement and ATP detection assay demonstrated LDHA inhibition notably decreased glucose consumption, lactate production and ATP levels in both HeLa and SiHa cells. Furthermore, the effect of LDHA inhibition on cell proliferation, cell cycle and apoptosis was investigated by MTT, BrdU incorporation, colony formation assay, flow cytometry and western blotting; LDHA knockdown or oxamate treatment led to decreased cell proliferation and increased apoptosis. Inhibition of LDHA induced G2/M cell cycle arrest and activated the mitochondrial apoptosis pathway. Mechanistically, the JNK signaling pathway was key for LDHA inhibition‑mediated cell cycle arrest and apoptosis. Collectively, these results indicated that LDHA was involved in cervical cancer pathogenesis and may be a promising therapeutic target for treatment.
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April-2022
Volume 47 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang W, Wang C, Hu X, Lian Y, Ding C and Ming L: Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells. Oncol Rep 47: 77, 2022.
APA
Zhang, W., Wang, C., Hu, X., Lian, Y., Ding, C., & Ming, L. (2022). Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells. Oncology Reports, 47, 77. https://doi.org/10.3892/or.2022.8288
MLA
Zhang, W., Wang, C., Hu, X., Lian, Y., Ding, C., Ming, L."Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells". Oncology Reports 47.4 (2022): 77.
Chicago
Zhang, W., Wang, C., Hu, X., Lian, Y., Ding, C., Ming, L."Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells". Oncology Reports 47, no. 4 (2022): 77. https://doi.org/10.3892/or.2022.8288