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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines
Yukihiro Hiraishi1, Takeshi Wada, Ken Nakatani
1Department of Oral and Maxillofacial Surgery, Wakayama Medical University, 811-1 Kimiidera, 641-8509 Wakayama, Japan. hiraishi@wakayama-med.ac.jp
Abstract:
Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.
Insights
Combining EGFR inhibitors with cisplatin may overcome cisplatin resistance in oral squamous cell carcinoma (OSCC). This strategy enhances treatment efficacy for oral cancer patients with acquired resistance to cisplatin therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Epidermal growth factor receptor (EGFR) plays a role in cancer cell biology and is a validated therapeutic target.
- EGFR signaling pathways are linked to cisplatin sensitivity, with inhibitors showing promise in cisplatin-refractory cancers.
Purpose of the Study:
- To investigate if an EGFR inhibitor can enhance cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines.
- To evaluate the combined effects of AG1478 (an EGFR tyrosine kinase inhibitor) and cisplatin on OSCC and cisplatin-resistant sublines.
Main Methods:
- Cultured OSCC cell lines and their cisplatin-resistant sublines were used.
- The effects of AG1478 alone and in combination with cisplatin were assessed.
- EGFR and phosphorylated EGFR (p-EGFR) expression levels were analyzed.
Main Results:
- Cisplatin-resistant OSCC cell lines exhibited higher expression of EGFR and p-EGFR compared to parental lines.
- The combination of AG1478 and cisplatin demonstrated augmented inhibition of OSCC cell growth in both cell lines.
Conclusions:
- Elevated EGFR and p-EGFR expression correlates with cisplatin resistance in OSCC.
- Combining EGFR inhibitors with cisplatin represents a potential therapeutic strategy for oral cancer patients with acquired cisplatin resistance.
