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Purpose <p>Immunochemotherapy is a promising strategy to enhance anticancer efficacy by combining immunomodulatory agents with conventional chemotherapy. Paclitaxel (PAX) is a widely used first-line chemotherapeutic agent for breast cancer, while LTX-315 is an oncolytic peptide with immunomodulatory properties. This study aimed to evaluate whether LTX-315 could potentiate the anticancer activity of paclitaxel in breast cancer models.</p> Methods <p>The combination of LTX-315 and paclitaxel was investigated in murine 4T1 and human MCF-7 breast cancer cell lines. Drug interactions were quantified using the Chou–Talalay method at fixed LTX-315 ratios of 1:2 and 2:1. Dose reduction index (DRI), cell migration, clonogenic survival, apoptotic nuclear morphology, and Annexin V-based apoptosis were assessed.</p> Results <p>Both 1:2 and 2:1 combinations showed synergistic interactions in MCF-7 cells, with cooperative activity also observed in 4T1 cells. DRI analysis revealed a favorable dose-sparing profile, with values ranging from approximately 4 to 22 at biologically relevant effect levels. Co-treatment with LTX-315 at 5 μM and paclitaxel at 0.25 μM significantly inhibited cell migration and reduced long-term clonogenic survival compared with single agents. Although apoptotic nuclear morphology was enhanced, early Annexin V-positive populations were not significantly increased.</p> Conclusion <p> LTX-315 potentiates paclitaxel activity through quantitative synergy, dose-sparing effects, and durable inhibition of breast cancer cell growth and migration, primarily via sustained functional growth suppression rather than amplification of early apoptosis.</p>

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Functional Synergism of LTX-315 and Paclitaxel in Breast Cancer Models

  • 期刊论文

  • 发表日期：

    2026年7月4日

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  • Thi Thu Phuong Tran,
  • Ngoc Anh Nguyen,
  • Thu Trang Nguyen,
  • Uyen Thi Tu Phan,
  • Huy Xuan Luong,
  • Tuan Hiep Tran

摘要

Purpose

Immunochemotherapy is a promising strategy to enhance anticancer efficacy by combining immunomodulatory agents with conventional chemotherapy. Paclitaxel (PAX) is a widely used first-line chemotherapeutic agent for breast cancer, while LTX-315 is an oncolytic peptide with immunomodulatory properties. This study aimed to evaluate whether LTX-315 could potentiate the anticancer activity of paclitaxel in breast cancer models.

Methods

The combination of LTX-315 and paclitaxel was investigated in murine 4T1 and human MCF-7 breast cancer cell lines. Drug interactions were quantified using the Chou–Talalay method at fixed LTX-315 ratios of 1:2 and 2:1. Dose reduction index (DRI), cell migration, clonogenic survival, apoptotic nuclear morphology, and Annexin V-based apoptosis were assessed.

Results

Both 1:2 and 2:1 combinations showed synergistic interactions in MCF-7 cells, with cooperative activity also observed in 4T1 cells. DRI analysis revealed a favorable dose-sparing profile, with values ranging from approximately 4 to 22 at biologically relevant effect levels. Co-treatment with LTX-315 at 5 μM and paclitaxel at 0.25 μM significantly inhibited cell migration and reduced long-term clonogenic survival compared with single agents. Although apoptotic nuclear morphology was enhanced, early Annexin V-positive populations were not significantly increased.

Conclusion

LTX-315 potentiates paclitaxel activity through quantitative synergy, dose-sparing effects, and durable inhibition of breast cancer cell growth and migration, primarily via sustained functional growth suppression rather than amplification of early apoptosis.