<p>Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer</p>

Abstract

Purpose: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo. Patients and Methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo. Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX. Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.

Identification of Antitumor Active Constituents in Polygonatum sibiricum Flower by UPLC-Q-TOF-MSE and Network Pharmacology

“…31 PIK3CG is an upregulated gene and a subunit of PI3K, which is closely related to various tumors. 32 AKT1 is a downregulated gene and is highly expressed in tumor tissues. It can participate in tumor metastasis.…”

Network pharmacology-based analysis for unraveling potential cancer-related molecular targets of Egyptian propolis phytoconstituents accompanied with molecular docking and in vitro studies

“…It is reported that PIK3CG is also a potential target for the treatment of few malignant tumors such as acute lymphoblastic leukemia, medulloblastoma and Kaposi sarcoma. 45 …”

“…It is reported that PIK3CG is also a potential target for the treatment of few malignant tumors such as acute lymphoblastic leukemia, medulloblastoma and Kaposi sarcoma. 45 The most signicant molecular functions were enzyme binding, RNA polymerase II transcription factor activity and transcription factor binding. Meanwhile, the most involved cellular components were cytosol, endoplasmic reticulum membrane and nucleus (Fig.…”

A New Computational Approach to Evaluating Systemic Gene–Gene Interactions in a Pathway Affected by Drug LY294002

“…For example, ribosomal protein S6 (RPS6) was associated with breast cancer by targeting miR-129-5p [36] and regulating PIK3CA [37]. Recent work suggested that PIK3CG was a targeted therapy for claudin-low breast cancer; we also found the quantitative target gene of the given drug [38]. The diagram shown in Figure 3 illustrates an aggregation of both negative and positive quality interactions presented in Table 2.…”