JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Amplification and overexpression of the c-Myc oncogene are prevalent in human ovarian cancers, indicating its potential as a therapeutic target.
• BET bromodomain (BRD) inhibitors, such as JQ1, have demonstrated anti-tumor activity in various cancer types.

Purpose of the Study:

• To investigate the efficacy of JQ1 as a therapeutic agent against ovarian cancer by targeting c-Myc.
• To explore the effects of JQ1 on ovarian cancer cell proliferation, cell cycle progression, apoptosis, and metabolism.

Main Methods:

• Utilized ovarian cancer cell lines, a transgenic mouse model, and primary human ovarian cancer tissues.
• Administered JQ1 to assess its impact on cellular proliferation, cell cycle arrest, and apoptosis.
• Analyzed the effects of JQ1 on the aerobic glycolysis pathway, including lactate dehydrogenase A (LDHA) activity and phosphorylation, and lactate production.

Main Results:

• JQ1 significantly suppressed ovarian cancer cell proliferation and induced cell cycle arrest and apoptosis in vitro and in vivo.
• JQ1 effectively targeted c-Myc in ovarian cancer models.
• JQ1 modulated cancer metabolism by inhibiting LDHA activity and phosphorylation, reducing lactate production and energy supply.

Conclusions:

• JQ1 demonstrates significant anti-tumor efficacy in ovarian cancer by targeting c-Myc.
• JQ1-induced effects include cell cycle arrest, apoptosis, and metabolic alterations, particularly in aerobic glycolysis.
• JQ1 represents a promising therapeutic candidate for ovarian cancer treatment.