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C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.


ABSTRACT:

Objectives

STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).

Methods

PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs.

Results

C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway.

Conclusions

In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

SUBMITTER: Zheng R 

PROVIDER: S-EPMC11342528 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

Zheng Rongji R   Guan Tian T   Hong Chaoqun C   Yao Yao Y   Fang Yutong Y   Huang Wei W   Chen Chunfa C   Zeng Huancheng H   Huang Jiman J   Lin Hui H   Chen Bingfeng B   Zhang Rendong R   Chen Dongmei D   Ding Zhechun Z   Zeng Haoyu H   Wu Jundong J  

Journal of translational medicine 20240822 1


<h4>Objectives</h4>STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).<h4>Methods</h4>PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient d  ...[more]

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