Related Experiment Video

Updated: Jun 15, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin

Masaki Shiota1, Akira Yokomizo, Eiji Kashiwagi

  • 1Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Cancer Science
|March 10, 2010
PubMed

Insights

Cisplatin resistance in advanced cancers can be overcome by targeting the Foxo3a transcription factor. Mithramycin enhances cisplatin sensitivity by increasing Foxo3a expression and acetylation, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cisplatin resistance is a significant challenge in treating advanced cancers.
  • The transcription factor Foxo3a regulates genes involved in DNA repair and apoptosis, crucial for chemotherapy response.

Purpose of the Study:

  • To investigate the role of Foxo3a in cisplatin resistance.
  • To explore the potential of mithramycin and Foxo3a modulation as a therapeutic strategy against cisplatin-resistant cancers.

Main Methods:

  • Comparative analysis of cisplatin-resistant and parental cancer cells.
  • Gene knockdown and overexpression studies of Foxo3a and p300.
  • Assessment of cell proliferation, cisplatin sensitivity, reactive oxygen species production, and Foxo3a acetylation.

Main Results:

  • Cisplatin-resistant cells exhibited decreased Foxo3a expression and increased sensitivity to mithramycin.
  • Mithramycin enhanced cisplatin sensitivity by upregulating Foxo3a expression via reactive oxygen species.
  • Foxo3a acetylation was reduced in resistant cells and upon cisplatin treatment; p300 knockdown promoted resistance.

Conclusions:

  • Foxo3a expression and acetylation are critical determinants of cisplatin sensitivity.
  • Inducing the Foxo3a pathway and promoting its acetylation represent promising therapeutic avenues for overcoming cisplatin resistance.
  • Mithramycin's efficacy is linked to Foxo3a activation, suggesting its potential role in novel cancer treatment regimens.

More Related Videos

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...