What is the clinical evidence from this study?

Study design: Other. Population: Ovarian cancer (n=104). Intervention: Adipocyte-conditioned medium vs. Carboplatin treatment alone. Primary outcome: IC50 of carboplatin (p=<0.01).

What does this research mean for the field?

Adipocyte-secreted ANGPTL4 promotes carboplatin resistance in ovarian cancer cells via integrin α5β1 activation of the c-myc/NF-κB pathway and upregulation of anti-apoptotic and ABC transporter proteins. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To elucidate the cellular and molecular mechanisms by which adipocytes confer carboplatin resistance to ovarian cancer cells.

June 16, 2020Oncology ReportsOpen Access

Adipocytes induce the resistance of ovarian cancer to carboplatin through ANGPTL4

Q: What are the key findings of this study?

Adipocyte-conditioned medium decreased the therapeutic effect of carboplatin on ovarian cancer cells, increasing the IC50 from 100.28 to 155.67 µg/ml.

Q: What does this research mean for the field?

Adipocyte-secreted ANGPTL4 promotes carboplatin resistance in ovarian cancer cells via integrin α5β1 activation of the c-myc/NF-κB pathway and upregulation of anti-apoptotic and ABC transporter proteins. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To elucidate the cellular and molecular mechanisms by which adipocytes confer carboplatin resistance to ovarian cancer cells.

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Key result

Adipocyte-conditioned medium reduces carboplatin efficacy in ovarian cancer cells, increasing IC50 by ~55%.

P<0.01
n=104

Why the study?

Carboplatin resistance restricts ovarian cancer treatment efficacy, but the association between adipocytes and ovarian cancer resistance has rarely been reported.

Does targeting adipocyte-derived ANGPTL4 reverse carboplatin resistance in ovarian cancer?

Design

In vivo and in vitro experimental study

Authors

SZSonghui ZhouJiangsu Province Hospital RWRuicheng WangGeorgia Institute of Technology HXHong XiaoArmy Medical University

Discussion

Member takes

Implication

Suggests adipocyte factors may reduce carboplatin efficacy in ovarian cancer models; leaves open ANGPTL4 targeting as a resistance strategy.

Key Points

To elucidate the cellular and molecular mechanisms by which adipocytes confer carboplatin resistance to ovarian cancer cells.
Conducted in vitro and in vivo assays paired with bioinformatics analysis to identify adipocyte-secreted factors that promote chemoresistance.
Employed cellular and molecular biological assays alongside forward and backward validation to delineate downstream signaling cascades and receptor-binding interactions.
Identified that adipocyte-secreted glycosylated ANGPTL4 binds integrin α5β1 on ovarian cancer cells to drive carboplatin resistance.
Demonstrated that ANGPTL4 activates the c-myc/NF-κB axis, upregulating antiapoptotic protein Bcl-xL and ABC transporter family members ABCB1, ABCC1, and ABCG2.

Structured PICO

Does targeting adipocyte-derived ANGPTL4 reverse carboplatin resistance in ovarian cancer?

Population

104 female SCID nude mice and human SKOV3 ovarian cancer cells used to evaluate adipocyte-induced carboplatin resistance.

Intervention

Adipocyte-derived ANGPTL4 / targeting ANGPTL4 combined with carboplatin

Outcome

Resistance to carboplatinsurrogate

Main Result

Absolute Event Rate: 155.67% vs 100.28%

p-value: p=<0.01

Targeting adipocyte-derived ANGPTL4 in combination with carboplatin may help overcome drug resistance in ovarian cancer.

Cite This Study

Zhou et al. (2020) studied Ovarian cancer (n=104). Adipocyte-conditioned medium vs. Carboplatin treatment alone was evaluated on IC50 of carboplatin (p=<0.01). Adipocyte-conditioned medium decreased the therapeutic effect of carboplatin on ovarian cancer cells, increasing the IC50 from 100.28 to 155.67 µg/ml.

synapsesocial.com/papers/6aa92ceebd8a0bf348461db9 https://doi.org/10.3892/or.2020.7647

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Implication

Suggests adipocyte factors may reduce carboplatin efficacy in ovarian cancer models; leaves open ANGPTL4 targeting as a resistance strategy.

Adipocytes induce the resistance of ovarian cancer to carboplatin through ANGPTL4

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Adipocytes induce the resistance of ovarian cancer to carboplatin through ANGPTL4

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider