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Supplementary Figures 1-11 from Suppression of MET Signaling Mediated by Pitavastatin and Capmatinib Inhibits Oral and Esophageal Cancer Cell Growth

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posted on 2023-04-03, 19:43 authored by Bo Xu, Tomoki Muramatsu, Johji Inazawa
<p>S1. The sensitivity to pitavastatin in OSCC and ESCC cell lines. S2. Pitavastatin suppresses the expression of cell cycle-related genes and induces DNA damage. S3. GGPS1 is a key regulator of cell growth. S4. GGPS1 expression might be correlated with sensitivity to statins. S5. DGBP, a GGPS1 inhibitor, inhibits tumor growth as well as pitavastatin. S6. MET expression is associated with poor prognosis in head and neck cancer. S7. Treatment with pitavastatin or knockdown of GGPS1 inhibited MET maturation. S8. The inhibition of MET maturation is caused by inhibition of the mevalonate pathway. S9. The combination of pitavastatin and capmatinib synergistically inhibits cell growth in vitro. S10. The combination of statins and capmatinib has a synergistic effect on cell growth inhibition. S11. Adding mevalonate or GGPP cancels the effect of the combination of pitavastatin and capmatinib on cell growth, and this combination synergistically enhances tumor growth inhibition in ovo and in vivo mouse models.</p>

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    DOI - Is supplement to Suppression of MET Signaling Mediated by Pitavastatin and Capmatinib Inhibits Oral and Esophageal Cancer Cell Growth

ARTICLE ABSTRACT

Despite increasing knowledge on oral and esophageal squamous cell carcinoma (OSCC and ESCC), specific medicines against both have not yet been developed. Here, we aimed to find novel anticancer drugs through functional cell-based screening of an FDA-approved drug library against OSCC and ESCC. Pitavastatin, an HMGCR inhibitor, emerged as an anticancer drug that inhibits tumor growth by downregulating AKT and ERK signals in OSCC and ESCC cells. One of the mechanisms by which pitavastatin inhibits cell growth might be the suppression of MET signaling through immature MET due to dysfunction of the Golgi apparatus. Moreover, the sensitivity of tumor growth to pitavastatin might be correlated with GGPS1 expression levels. In vivo therapeutic models revealed that the combination of pitavastatin with capmatinib, a MET-specific inhibitor, dramatically reduced tumor growth. Our findings suggest that GGPS1 expression could be a biomarker in cancer therapy with pitavastatin, and the combination of pitavastatin with capmatinib might be a promising therapeutic strategy in OSCC and ESCC. This study provides new insight into the mechanism of pitavastatin as an anticancer drug and suggests that the combination of pitavastatin with capmatinib is a useful therapeutic strategy in OSCC and ESCC.

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