Synergistic therapeutic effects of pertuzumab and pyrrolitinib in HER-2-positive breast cancer: modulation of the PI3K/AKT pathway
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Pertuzumab and pyrrolizinib target HER-2 (human epidermal growth factor receptor 2) to inhibit breast cancer cell growth. This combination therapy downregulates the PI3K/AKT signaling pathway, offering a potential new treatment strategy.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Human epidermal growth factor receptor 2 (HER-2) is frequently overexpressed in breast cancer, driving tumor growth and progression.
- Targeted therapies aim to inhibit specific molecular pathways involved in cancer development.
- Understanding the synergistic effects of drug combinations is crucial for developing effective breast cancer treatments.
Purpose Of The Study
- To elucidate the mechanism of action of pertuzumab in combination with pyrrolitinib for breast cancer treatment.
- To investigate the role of HER-2 and the PI3K/AKT pathway in the efficacy of this drug combination.
Main Methods
- Real-time PCR and Western blot (WB) were used to assess HER-2 expression in breast cancer cells.
- BT-474 cells were treated with varying concentrations of pertuzumab, pyrrolitinib, or their combination.
- Cell viability, migration, invasion, and apoptosis were evaluated using CCK-8, colony formation, wound healing, Transwell assays, and TUNEL assays. KEGG pathway analysis and String database were employed to analyze signaling pathways.
Main Results
- Elevated HER-2 expression was confirmed in breast cancer cells.
- The combination of pertuzumab and pyrrolitinib significantly reduced HER-2 levels, inhibited cell viability, proliferation, migration, and invasion, while promoting apoptosis.
- HER-2 knockdown mimicked these effects and downregulated PI3K/AKT signaling, which was reversed by IGF-1.
Conclusions
- Pertuzumab and pyrrolitinib act by targeting HER-2, leading to the downregulation of the PI3K/AKT signaling pathway.
- This targeted inhibition effectively suppresses breast cancer cell proliferation, migration, and invasion.
- The findings support the potential of this combination therapy for breast cancer treatment.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...