# Combination with a Low Dose of Doxorubicin Further Boosts the Antitumor Effect of SLURP-1 In Vivo and Associates with EGFR Down-Regulation

## TL;DR

Combining low-dose doxorubicin with SLURP-1 enhances anti-tumor effects in skin cancer by reducing EGFR activity and metastasis without toxicity.

## Contribution

A novel combination therapy using low-dose doxorubicin and SLURP-1 is shown to boost anti-tumor efficacy in SCC.

## Key findings

- Combining SLURP-1 with low-dose doxorubicin significantly enhances anti-tumor activity in SCC.
- The combination therapy suppresses metastasis and down-regulates EGFR expression in tumors.
- The treatment is effective without causing toxicity in the studied model.

## Abstract

Skin cancers such as squamous cell carcinoma (SCC) are among the most
aggressive types of tumors. They come with a high rate of growth, metastasis,
and frequently occurring chemoresistance. Smoking is one of the risk factors
for SCC progression, and the α7 nicotinic acetylcholine receptor
(α7-nAChR) is a promising target for SCC therapy. Human secreted protein
SLURP-1 is an auto/paracrine regulator of epithelial homeostasis and a
selective negative allosteric modulator of α7-nAChR. Recently, we
demonstrated the high efficiency of the therapy based on the recombinant
SLURP-1 in controlling SCC cell growth and metastasis in vivo.
The anti-tumor effect of SLURP-1 was mediated through interaction with both
α7-nAChR and the epidermal growth factor receptor (EGFR). Cytotoxic
antibiotic doxorubicin has been proposed for the SCC therapy; however, its use
is limited due to the high toxicity. In this study we investigated the use of
an enhanced SLURP-1 dose and of a combination of SLURP-1 with low-dozen
doxorubicin for SCC treatment of mice xenografted with squamous cell carcinoma
A431 cells. An increased SLURP-1 dose didn’t significantly enhance the
efficiency of the therapy. However, the combination with doxorubicin further
enhanced the anti- tumor activity of SLURP-1 and dramatically suppressed
metastasis. The effect from the combined therapy was accompanied by
down-regulation of EGFR expression in tumors. Direct inhibition of EGFR
activation by SLURP-1 was shown. No toxicity of the combined therapy was
encountered. Our data indicate that the combination of SLURP-1 with
chemotherapy in lower doses is a promising approach in SCC treatment and should
be further studied.