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BACKGROUND: Growth differentiation factor 15 (GDF15), a member of the transforming growth factor beta (TGF-ß) superfamily, is involved in various pathophysiological processes such as anorexia, obesity, inflammation, and tumorigenesis. However, the role of GDF15 in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: Clinical significance of GDF15 in ccRCC as well as other types of human cancers was analyzed using the TCGA PANCAN dataset. Gene Set Enrichment Analysis (GSEA) was used to study the significantly enriched pathways associated with GDF15 expression. qRT-PCR was used to quantitatively assess relative mRNA expression level. Flow cytometry was used to detect cell cycle. CCK-8 assay, colony formation assay, wound healing assay, Transwell migration/invasion assay, and EdU assay were used to comprehensively examine tumor viability and aggressiveness. MDA and iron assays were used to determine ferroptosis-related intracellular changes. RESULTS: We found that GDF15 expression is decreased in renal carcinoma tissue. In 769-p and Caki-1 cells, GDF15 knockdown significantly promoted tumor viability, proliferation, and migration. Conversely, overexpression of GDF15 suppressed cell proliferation and invasion. Results from GSEA suggested that GDF15 might play a crucial role in ferroptosis. We further demonstrated that GDF15 is correlated with intracellular iron and lipid peroxidation MDA in 769-p and Caki-1 cells. In summary, we conclude that GDF15 inhibits migration and invasion of ccRCC cells by regulating ferroptosis. CONCLUSION: Our study demonstrates that GDF15 downexpression promotes viability and aggressiveness of ccRCC cells by abolishing ferroptosis, which confers unfavorable patient survival outcomes.
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Aims The aim of this study was to investigate the anti-tumor efficacy of brucine on intrahepatic cholangiocarcinoma (ICC). Methods ICC QBC939 cells were treated with brucine, cell viability, cell cycle and apoptosis were analyzed using CCK-8 and flow cytometry. The expression of COX-2 and apoptosis related proteins Casp3, Bax and Bcl-2 were detected by Western blot analysis. QBC939 cells were subcutaneously transplanted into nude mice and the mice were injected with brucine intraperitoneally. The expression of Ki67, COX-2 and apoptosis related proteins were detected by immunohistochemical staining and Western blot analysis. Results Brucine significantly inhibited the proliferation and cell cycle progression while promoted the apoptosis of QBC939 cells. The expression of the apoptotic proteins Casp3 and Bax was upregulated, while the expression of Bcl-2 and COX-2 was downregulated in QBC939 cells with brucine treatment. Moreover, the overexpression of COX-2 could antagonize the effects of brucine on QBC939 cells. In vivo, brucine inhibited subcutaneous tumor formation in nude mice, and the expression of Ki67, COX-2 and Bcl-2 decreased while the expression of Casp3 and Bax increased in tumor tissues from nude mice with brucine treatment. Conclusions Brucine can significantly inhibit the progression of cholangiocarcinoma in vitro and in vivo, and the mechanism may be related to the inhibition of COX-2 expression.
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A case of a papillary thyroid carcinoma in a patient with situs inversus with associated bronchiectasis and chronic sinusitis (Kartagener's syndrome) is reported. A 61-year-old male patient has the symptoms of nasal obstruction. nasal purulent discharge and headache for 2 years. Physical examination: right nasal purulent in right nasal cavity and multiple lychee-like opaque mass in right middle meatus. A nodule, one centimeter in diameter, locates in the upper pole of right thyroid. Evidence of full situs inversus viscerum can be confirmmed by chest radiographs and ultrasound doppler. Pathology: right nasal polyps, the right small papillary thyroid cancer. TEM Tip primary ciliary dyskinesia. Clinical diagnosis: Kartagener syndrome, papillary thyroid carcinoma (T1a N0 M0, I period), chronic sinusitis-nasal polyps.
