Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma

Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Ohnishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

Research output: Contribution to journalArticle

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Abstract

Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

Original languageEnglish
Pages (from-to)2576-2582
Number of pages7
JournalOncology Reports
Volume35
Issue number5
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Transcription Factor 3
Fluorouracil
Cisplatin
Hepatocellular Carcinoma
Multidrug Resistance-Associated Proteins
Immunoblotting
Small Interfering RNA
Stomach Neoplasms
Neoplasms
Proteins
Complementary DNA
Drug Therapy
Cell Line

Keywords

  • 5-fluorouracil
  • Chemoresistance
  • Cisplatin
  • Hepatocellular carcinoma
  • Multidrug resistance-associated protein
  • Runt-related transcription factor 3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma. / Kataoka, Junro; Shiraha, Hidenori; Horiguchi, Shigeru; Sawahara, Hiroaki; Uchida, Daisuke; Nagahara, Teruya; Iwamuro, Masaya; Morimoto, Hiroki; Takeuchi, Yasuto; Kuwaki, Kenji; Ohnishi, Hideki; Nakamura, Shinichiro; Takaki, Akinobu; Nouso, Kazuhiro; Yagi, Takahito; Yamamoto, Kazuhide; Okada, Hiroyuki.

In: Oncology Reports, Vol. 35, No. 5, 01.05.2016, p. 2576-2582.

Research output: Contribution to journalArticle

Kataoka, Junro ; Shiraha, Hidenori ; Horiguchi, Shigeru ; Sawahara, Hiroaki ; Uchida, Daisuke ; Nagahara, Teruya ; Iwamuro, Masaya ; Morimoto, Hiroki ; Takeuchi, Yasuto ; Kuwaki, Kenji ; Ohnishi, Hideki ; Nakamura, Shinichiro ; Takaki, Akinobu ; Nouso, Kazuhiro ; Yagi, Takahito ; Yamamoto, Kazuhide ; Okada, Hiroyuki. / Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma. In: Oncology Reports. 2016 ; Vol. 35, No. 5. pp. 2576-2582.
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AU - Uchida, Daisuke

AU - Nagahara, Teruya

AU - Iwamuro, Masaya

AU - Morimoto, Hiroki

AU - Takeuchi, Yasuto

AU - Kuwaki, Kenji

AU - Ohnishi, Hideki

AU - Nakamura, Shinichiro

AU - Takaki, Akinobu

AU - Nouso, Kazuhiro

AU - Yagi, Takahito

AU - Yamamoto, Kazuhide

AU - Okada, Hiroyuki

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