2D-DIGE Proteomic Analysis of Changes in Estrogen/Progesterone-Induced Rat Breast Hyperplasia upon Treatment with the Mongolian Remedy RuXian-I

Abstract

RuXian-I has traditionally been used as a remedy for breast hyperplasia in the Inner Mongolia Autonomous Region of China. As a first step toward the investigation of biomarkers associated with RuXian-I treatment, a proteome-wide analysis of rat breast tissue was conducted. First, rat breast hyperplasia was induced by injection of estradiol and progesterone. After treatment with RuXian-I, there is a marked decrease in the hyperplasia, as can be shown by decreases in the nipple diameter and the pathological changes in breast. Subsequently, we used an approach that integrates size-based 2D-DIGE, MALDI-TOF/TOF-MS, and bioinformatics to analyze data from the control group, the model group and the RuXian-I treatment group. Using this approach, seventeen affected proteins were identified. Among these, 15 (including annexin A1, annexin A2, superoxide dismutase [Mn], peroxiredoxin-1, translationally-controlled tumor protein and α B-crystallin) were significantly up-regulated in the model group and down-regulated upon treatment with RuXian-I, and two (Tpil protein and myosin-4) have the opposite change trend. The expression of annexin A1 was confirmed using immunohistochemistry. The expression of superoxide dismutase (SOD) activity was confirmed biochemically. These results indicated that RuXian-I treats rat breast hyperplasia through regulation of cell cycle, immune system, metabolic, signal transduction, etc. The differential expressions of these proteins (annexin A1, superoxide dismutase [Mn], alpha B-crystallins and translationally controlled tumor protein, among others) were associated with occurrence and metastasis of breast cancer. These findings might provide not only far-reaching valuable insights into the mechanism of RuXian-I action, but also leads for prognosis and diagnosis of breast hyperplasia and breast cancer.

Exosomes and development of cancer cell resistance to metformin: pilot study

“…Среди последних выявлены 7 белков, диффе-ренциально экспрессированных в экзосомах клеток MCF-7М по сравнению с клетками MCF-7, в их числе 3 белка с выраженными антиапоптотическими / цито-протективными свойствами: Complement C1q tumor necrosis factor-related protein 3 [11], Hornerin [12], myosin 4 [13].…”

Annexin A2: The Importance of Being Redox Sensitive

“…One study investigated the effect of the Mongolian remedy RuXian-I in the treatment of breast hyperplasia [103]. Rats were either mock treated (control group), injected with estradiol and progesterone to induce breast hyperplasia (model group) or treated with RuXian-I after induction of breast hyperplasia.…”

“…Subsequently, the authors used an approach that integrated size-based 2D-DIGE, MALDITOF/TOF-MS and bioinformatics to analyze data from the control group, the model group and the RuXian-I-treated group. Fifteen proteins were upregulated, including annexin A2, annexin A1, superoxide dismutase [Mn], peroxiredoxin-1, translationally-controlled tumour protein and α B-crystallin in the model group compared to the control group and downregulated upon treatment with RuXian-I [103]. Multiple biological activities have been reported for the main components of RuXian-I.…”

Therapeutic Effect of Mongolian Medicine RuXian‐I on Hyperplasia of Mammary Gland Induced by Estrogen/Progesterone through CRYAB‐Promoted Apoptosis

“…erefore, it has a very good effect on breast hyperplasia in women [8,9]. Although there is a good effect, little is known about the mechanism.…”