Potential Treatment for Advanced Kidney Cancer

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Renal cell carcinoma (RCC), the most common type of kidney cancer, is aggressive and frequently develops resistance to therapy. Advanced RCC has a poor prognosis and new, effective treatment strategies are badly needed. Metastatic RCC may be treated with sunitinib, but the majority of cancers eventually develop resistance to this drug. Sunitinib inhibits signaling through receptor tyrosine kinases, interfering with pro-growth signals received by the tumor.

In a recent publication, Markowitsch et al investigated the effect of shikonin (SHI) on sunitinib-sensitive and sunitinib-resistant RCC cell lines in cell culture. SHI is a naturally occurring compound. It’s an active component of a dried plant root (Lithospermum erythrorhizon) that has been used in traditional Chinese medicine to address a variety of ailments.

Earlier studies have demonstrated the anti-cancer capabilities of SHI and have shown that SHI can enhance the activity of traditional chemotherapeutics or re-sensitize chemotherapy-resistant cells to therapy. How SHI exerts these effects is not clear; however, as SHI has been found to affect many cell signaling pathways and induce cell death via apoptosis and necroptosis.

The recent work by Markowitsch et al thoroughly examined the effect of SHI on many aspects of RCC cell biology. Several assays relied on imaging with the Azure Sapphire Biomolecular Imager, including studies that characterized protein expression related to multiple signaling pathways by Western blot, adhesion of RCC cells to extracellular matrix proteins and to vascular endothelial cells, and studies of tumor cell migration and chemotaxis, relied on imaging with the Sapphire.

Figure 2 from Markowitsch et al. (2022) Shikonin inhibits cell growth of sunitinib-resistant renal cell carcinoma by activating the necrosome complex and inhibiting the AKT/mTOR signaling pathway. Licensed under CC BY 4.0. The Azure Biomolecular Imager was used to image and quantify RCC colonies on cell culture dishes.

The authors took advantage of several imaging modes provided by the Sapphire. The Sapphire was used to image and quantify the growth of colonies in 6-well culture dishes using Coomassie Blue dye detection. The Sapphire was used to assess cell adhesion, chemotaxis and cell motility by measuring the fluorescence of cells labeled with CellTracker Green in either pre-treated 24-well culture dishes or on the lower surface of membrane inserts in 24-well plates. Western blots were detected using enhanced chemiluminescence and imaged on the Sapphire.

The results of the numerous studies indicated that, though the specific effects varied by cell line, SHI had antitumor effects on all cell lines studied. SHI was found to inhibit RCC cell growth, proliferation, and clone formation, both in sunitinib-sensitive and sunitinib-resistant cell lines. SHI caused cell cycle arrest and induced cell death, primarily via necroptosis. SHI also inhibited the AKT/mTOR pathway, which presents another mechanism by which SHI may interfere with RCC cell survival and growth.

The authors conclude the data is promising and that SHI should be further studied as a potential addition to therapy for patients with advanced and therapy-resistant RCC.

In addition to visible and fluorescent imaging of tissue culture plates, and chemiluminescent imaging of Western blots, the Sapphire Biomolecular Imager provides densitometry, phosphor, multichannel fluorescence, near-infrared, and white light imaging of blots, gels, tissues, and more. Learn more about the Sapphire Imager and how Azure can support your research by clicking here.

 

Explore: Azure Sapphire Biomolecular Imager

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