Effects of modified Shu-Gan-Liang-Xue decoction combined with anastrozole on osteoblastic proliferation and differentiation of MC3T3-E1 cells

Abstract

Aromatase inhibitors (AIs) are widely used in the treatment of hormone-dependent breast cancer and as a result, aromatase inhibitor-associated bone loss (AIBL) has become a major concern amongst patients receiving AI treatment. Modified Shu-Gan-Liang-Xue decoction (mSGLXD), a clinical prescription, has been used for ameliorating AIBL in patients with breast cancer for decades and has achieved good clinical efficacy. However, the mechanism underlying how mSGLXD influences bone homeostasis and alleviates AIBL has remained elusive. In the present study, mSGLXD was supplemented with Rhizoma Drynariae containing phytoestrogens, and the safety of mSGLXD was evaluated. mSGLXD did not possess estrogenic activity and significantly inhibited the proliferation of estrogen receptor-positive breast cancer cell line MCF-7, which suggested that mSGLXD was safe for postmenopausal patients with breast cancer. Subsequently, the effects of mSGLXD alone or in combination with anastrozole on osteoblastic MC3T3-E1 cell proliferation and differentiation were investigated. Cell counting kit-8, reverse transcription-polymerase chain reaction and biochemical methods, such as ELISA and alizarin red S staining, were used in the present study. It was revealed that mSGLXD not only stimulated MC3T3-E1 cell proliferation, but also upregulated alkaline phosphatase and osteocalcin gene and protein expression levels. High concentrations of anastrozole (10 or 100 μmol/l) markedly inhibited MC3T3-E1 cell proliferation, but this inhibitory effect was attenuated by mSGLXD. Furthermore, mSGLXD increased MC3T3-E1 cell mineralization following β-glycerophosphate and ascorbic acid induction. Therefore, the results of the present study suggested that mSGLXD may be a promising adjuvant therapy, with high safety and efficacy, for the prevention and treatment of AIBL in patients with breast cancer who receive AI treatment.

Chinese Herbal Medicine to Alleviate Vasomotor Symptoms in Breast Cancer Survivors: A Study Protocol for a Randomised, Double Blind, Placebo Controlled, Multi Centre, Cross Over Trial

“…Appropriate safety of SGLXD has been shown in herb-drug safety/interaction studies [39,59,73,[76][77][78][79][80][81][82][83][84][85][86][87][88][89]. This preliminary research has been limited to China, with Chinese breast cancer survivors and in a Chinese hospital setting.…”

Chinese Medicines Improve Perimenopausal Symptoms Induced by Surgery, Chemoradiotherapy, or Endocrine Treatment for Breast Cancer

“…Experimental studies have confirmed that Shugan Liangxue Decoction reduced tumor volumes in nude mice with or without ovariectomies. The decoction was also shown to dose-dependently downregulate proliferation of estrogen receptor (ER)-positive breast cancer cells (Fu and Li, 2011 ; Zhou et al, 2014 ) and with no significant estrogenic activity (Zhang and Li, 2009 ; Zhou et al, 2015 ). Its antitumor activity may be related to its inhibiting key estrogen synthetase, such as aromatase and steroid sulfatase (STS) (Zhang and Li, 2010 ; Zhou et al, 2014 ), and may also be related to its selective inhibition of estrogen receptor alpha (ERα) (Zhou et al, 2018 ).…”

“…In vivo studies in mice have shown a synergistic effect when Shugan Liangxue Decoction is used with tamoxifen, as it enhances anti-tumor effect of tamoxifen (Wu and Li, 2008 ) and alleviates tamoxifen's side effects on endometrial thickening (Li et al, 2003 ). In addition, Shugan Liangxue Decoction combined with anastrozole promotes osteoblast proliferation, enhances osteogenesis (Zhou et al, 2015 ), and improves bone metabolism (Liu et al, 2009 ), suggesting that Shugan Liangxue Decoction may improve bone loss caused by endocrine drugs.…”

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause

“…Aromatase inhibitors (AIs) are commonly used drugs for the treatment of hormone-sensitive breast cancer in postmenopausal females ( 1 ). AIs limit the extra-ovarian production of estrogens, which occurs in fat, the liver and muscles via the aromatization of androgens.…”