Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar 31:12:78.
doi: 10.1186/1477-7819-12-78.

Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: its implication for treatment

Yaping Yu, Minqi Liao, Ruiwen Liu, Jian Chen, Hao Feng, Zan Fu  1
Affiliations

Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: its implication for treatment

Yaping Yu et al. World J Surg Oncol. .

Abstract

Background: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is strongly expressed in several malignancies, that LDH-A expression is associated with poor prognosis, and that LDH-A inhibition severely diminishes tumorigenicity. However, little is known about the implications of LDH-A expression in intrahepatic cholangiocarcinoma. The purpose of this study was to investigate the expression of LDH-A and to clarify its effect on intrahepatic cholangiocarcinoma.

Methods: We studied the expression of LDH-A in tissue samples from patients with intrahepatic cholangiocarcinoma (n = 54) using the ultrasensitive surfactant protein (S-P) immunohistochemical method. We then inhibited LDH-A using small hairpin RNA (shRNA) in the cholangiocarcinoma cell line HuCCT-1 in vitro to study the role it plays in promoting growth and escaping apoptosis.

Results: We report that LDH-A was overexpressed in 52 of 54 (96%) paraffin-embedded cancer tissue samples and 0 of 54 para-carcinoma tissue samples. Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and induced apoptosis in HuCCT-1 cells. This result correlated with the elevation of cytoplasmic reactive oxygen species (ROS) levels.

Conclusions: LDH-A expression is closely correlated with histopathological variables of intrahepatic cholangiocarcinoma, indicating that LDH-A may serve as a new treatment target.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Immunohistochemical staining of lactate dehydrogenase-5 (LDH-A) in (A) para-carcinoma tissue and (B) tissue sections from human ICC. (B) Corresponding (original magnification, 200×). (A) Weak cytoplasmic and nuclear expression. (B) Strong cytoplasmic and nuclear expression. ICC, intrahepatic cholangiocarcinoma.
Figure 2
Figure 2
Knock-down of LDH-A inhibits growth and induces apoptosis in the HuCCT-1 cell line. (A) LDH-A expression was analyzed after transfection by RT-PCR, with actin as loading control. The figure shows that RNAi induced a specific decrease in LDH-A expression after transfection. (B) Western blot assay also shows a specific decrease in LDH-A expression after transfection, with actin as loading control. LDH-A, lactate dehydrogenase A; RNAi, RNA interference.
Figure 3
Figure 3
LDH-A knockdown inhibits HuCCT-1 cell growth. Relative cell numbers at 72 and 96 hours post-transfection for RNAi versus NC have a P value of 0.008 and 0.004, respectively. LDH-A, lactate dehydrogenase A; NC, negative control; RNAi, RNA interference.
Figure 4
Figure 4
Cell death was determined by flow cytometry of annexin V- and 7-AAD-stained cells at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). The histogram (right) represents the average percentage (±SD) of dead cells. The number of dead cells treated with shLDH-A (RNAi) compared with the control group (NC) has a P value of <0.05 using Student’s t test. 7-ADD, 7-aminoactinomycin D; RNAi, RNA interference; SD, standard deviation; sh, small hairpin.
Figure 5
Figure 5
Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). DCFDA, dichlorofluorescin diacetate; RNAi, RNA interference; ROS, reactive oxygen species; sh, short hairpin.
See this image and copyright information in PMC

References

    1. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer. 2002;2:10. doi: 10.1186/1471-2407-2-10. - DOI - PMC - PubMed
    1. Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, Clark JW, Abrams TA, Chan JA, Enzinger PC, Bhargava P, Kwak EL, Allen JN, Jain SR, Stuart K, Horgan K, Sheehan S, Fuchs CS, Ryan DP, Sahani DV. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11:48–54. doi: 10.1016/S1470-2045(09)70333-X. - DOI - PubMed
    1. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–1281. doi: 10.1056/NEJMoa0908721. - DOI - PubMed
    1. Warburg O. On the origin of cancer cells. Science. 1956;123:309–314. doi: 10.1126/science.123.3191.309. - DOI - PubMed
    1. Granchi C, Bertini S, Macchia M, Minutolo F. Inhibitors of lactate dehydrogenase isoforms and their therapeutic potentials. Curr Med Chem. 2010;17:672–697. doi: 10.2174/092986710790416263. - DOI - PubMed

Publication types

MeSH terms