Wnt5a peptides in reduction of cancer stem cells

A cancer stem cell and cancer technology, applied in the direction of medical preparations containing active ingredients, peptide sources, animal/human peptides, etc., can solve problems affecting stem cells, increase side effects, and improve cancer treatment effects

Pending Publication Date: 2020-07-14
ウィントリサーチアーベー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Finally, when targeting drugs to CSCs, there is a risk of affecting normal stem cells because CSCs have the same expression profile as normal stem cells

Method used

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  • Wnt5a peptides in reduction of cancer stem cells
  • Wnt5a peptides in reduction of cancer stem cells
  • Wnt5a peptides in reduction of cancer stem cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093]Tumors from two different human colon cancer cell types, HT29 and Caco-2 cells, were examined by immunohistochemistry (IHC) and mRNA (see figure 1 ).

[0094] On day 0: HT29 or Caco-2 colon cancer cells were injected subcutaneously in nude mice.

[0095] On day 7 after tumor establishment in mice, vehicle (saline) alone (gr 1 ) or Foxy-5 (2 μg / g; gr 2) was injected intraperitoneally (I.P).

[0096] Tumor growth and animal body weights were monitored on days 9-23 - then +8 I.P. injections of vehicle alone (gr 1 ) or Foxy-5 (2 μg / g; gr 2) every two days.

[0097] On day 24, two types of tumors (Caco-2 and HT29-derived) (divided into two fractions, one of which was fixed and the other frozen at -80°C) were analyzed by IHC for COX-2, 15PGDH, Protein expression of β-catenin, Ascl2, ALDH and Dckl1 and their mRNA contents of ALDH and Dckl1 (ALDH is a general stem cell marker and Dck1 is a specific marker of colonic CSCs).

[0098] Foxy-5 was shown to significantly reduce the...

Embodiment 2

[0100] For further verification Figures 2 to 4 Based on the findings outlined in, we analyzed the possible mechanisms responsible for the reduction in CSC numbers in this experiment. In colon cancer, the cyclooxygenase 2 (COX-2) enzyme is frequently upregulated. COX-2 activity leads to the production and release of prostaglandin E2 (PGE2). PGE2 promotes cancer progression and was shown to favor the expansion of colonic CSCs. (Wang et al., Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice[Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice]. Gastroenterology [Gastroenterology] 149:1884-1895, 2015) . While perturbation of the canonical WNT signaling pathway is thought to be the cause of colorectal tumors, the increased expression of cyclooxygenase 2 (COX-2) that occurs in most colorectal tumors is thought to play a role in colorectal cancer development. Crucial role. Increased COX-2 expression leads to...

Embodiment 3

[0102] The in vivo effects of Foxy-5 treatment on β-catenin signaling in HT-29 or Caco-2 colon cancer tissues may be another possible explanation for the observed reduction in CSC numbers. A reduction in the amount of active β-catenin nuclear expression was observed in both Caco-2 and HT29-derived colon cancer tumors as a result of Foxy-5 treatment (see Figure 7 with 8 ). The observation of decreased β-catenin signaling by Foxy-5 was confirmed by a reduction in tumor volume ( Image 6 with 7 ). Essential to this study is the fact that a Foxy-5-induced decrease in the β-catenin downstream target Ascl2, a transcription factor that promotes the cancer stem cell niche, was also observed, indicating the ability of Foxy-5 treatment to reduce CSC numbers Also depends on reduced β-catenin / Ascl2 signaling (see Figures 6 to 9 ). Thus, the Foxy-5 peptide exhibits the unique property of reducing CSC numbers through its ability to target three distinct elements (COX-2, 15-PGDH, and...

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Abstract

A peptide derived from WNT5A protein, said peptide being for use in the prevention of recurrence or relapse of a cancer in a patient or for use in the reduction or elimination of cancer stem cells ina patient diagnosed with a cancer.

Description

[0001] The present invention relates to WNT5A-derived peptides for preventing recurrence or recurrence of cancer in a patient or for reducing or eliminating cancer stem cells in a patient diagnosed with cancer. Background technique [0002] Primary tumors are rarely the cause of death in cancer patients. In most cases, death was the result of cancer recurrence following surgical removal of the primary tumor with variable recurrence-free survival. Current treatments for patients with breast, colon or prostate cancer include surgery, chemotherapeutic drugs, endocrine therapy and some novel biological treatments. The latter treatment modality primarily targets proliferative cancer cells and thus cancer growth. Although these treatments have a favorable effect on the primary tumor itself and most tumor cells remaining after surgery, a significant proportion of patients subsequently relapse. [0003] The underlying cause of this cancer recurrence is the presence of a subset of tu...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P35/00
CPCA61K38/1709A61P35/00A61K31/513A61K31/519A61K31/555A61K31/337A61K31/704C07K14/47A61K2300/00A61K38/04A61K45/05
Inventor 安尼塔·斯杰兰德
Owner ウィントリサーチアーベー
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