Abstract:
:Radiotherapy (RT) is one of the major modalities for non‑small cell lung cancer (NSCLC), but its efficacy is often compromised by cellular resistance caused by various mechanisms including the overexpression of epidermal growth factor receptor (EGFR). Although cis‑diamminedichloroplatinum(Ⅱ) (cisplatin, CDDP) has been well characterized as an effective radiosensitizer, its clinical application is limited by its severe nephrotoxic effects. In our current study, we developed a CDDP‑incorporated liposome (LP) conjugated with EGFR antibodies (EGFR:LP‑CDDP) and evaluated its potential to radiosensitize EGFR‑overexpressing cells without exerting nephrotoxic effects. EGFR:LP‑CDDP showed higher cytotoxicity than non‑targeting liposomal CDDP (LP‑CDDP) in the cells expressing EGFR in vitro. In an A549 cell‑derived xenograft tumor mouse model, increased delays in tumor growth were observed in the mice treated with a combination of EGFR:LP‑CDDP and radiation. Notably, the EGFR:LP‑CDDP‑treated animals showed no differences in body weight loss, survival rates of nephrotoxicity compared with untreated control mice. In contrast, the use of CDDP caused lower body weights and poorer survival outcomes accompanied by a significant level of nephrotoxicity [e.g., decreased kidney weight, increased blood urea nitrogen (BUN) and creatinine, and pathological change]. These findings suggest the feasibility of using EGFR:LP‑CDDP to radiosensitize cells in a targeted manner without inducing nephrotoxic effects. This compound may therefore have clinical potential as part of a tailored chemoradiotherapy strategy.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Jung J,Jeong SY,Park SS,Shin SH,Ju EJ,Choi J,Park J,Lee JH,Kim I,Suh YA,Hwang JJ,Kuroda S,Lee JS,Song SY,Choi EKdoi
10.3892/ijo.2014.2806subject
Has Abstractpub_date
2015-03-01 00:00:00pages
1268-74issue
3eissn
1019-6439issn
1791-2423journal_volume
46pub_type
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