Abstract
Increased glycolysis is considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during therapeutic resistance development is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we find that cisplatin-resistant cells exhibit increased fatty acids (FA) uptake, accompanied by decreased glucose uptake and lipogenesis, indicating reprogramming from glucose to FA dependent anabolic and energy metabolism. A metabolic index incorporating glucose derived anabolism and FA uptake correlates linearly to the level of cisplatin resistance in ovarian cancer (OC) cell lines and primary cells. The increased FA uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing beta-oxidation. Consequently, blocking beta-oxidation by a small molecule inhibitor combined with cisplatin or carboplatin synergistically suppresses OC proliferation in vitro and growth of patient-derived xenografts in vivo. Collectively, these findings support a rapid detection method of cisplatin-resistance at single cell level and a strategy for treating cisplatin-resistant tumors.
| Original language | English (US) |
|---|---|
| Article number | 4554 |
| Journal | Nature communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2022 |
Funding
This work was supported by R01CA224275 to DM and JXC and R33CA223581 and R35GM136223 to JXC. Research reported in this publication was supported by the Boston University Micro and Nano Imaging Facility and the Office of the Director, National Institutes of Health of the National Institutes of Health under award Number S10OD024993. PDX experiments were performed in the Northwestern University –Center for Developmental Therapeutics supported by the Cancer Center Support Grant NCI CA060553.
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy
