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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제28권 제1호
- 발행연도
- 2024.1
- 수록면
- 83 - 91 (9page)
- DOI
- 10.4196/kjpp.2024.28.1.83
이용수
초록· 키워드
오류제보하기
Hypoxia-inducible factor-1 alpha (HIF-1α ) is a transcription factor acti - vated under hypoxic conditions, and it plays a crucial role in cellular stress regulation.
While HIF-1 α activity is essential in normal tissues, its presence in the tumor microen - vironment represents a significant risk factor as it can induce angiogenesis and con - fer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1 α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1 α even un - der normoxia. In this study, we observed an inclination toward increased normoxic HIF-1 α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1 α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF- 1 α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a sig - nificant reduction in HIF-1 α expression upon HDAC6 inhibition. Moreover, the down - regulation of HIF-1 α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also dem - onstrated an inhibitory effect on cell invasion and migration by reducing HIF-1 α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1 α expression under normoxia, thereby suppressing the epithelial– mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer
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