Abstract
Shenling Baizhu additive powder (SLBZ-AP), a formulation of a variety of natural medicinal plants, has clinical efficacy in treating cancers in previous studies. We explored the effect of SLBZ-AP in bone metastasis of lung cancer (BMLC) mice, and the possible mechanism involved was further investigated in the present study. Mice model of BMLC was made and treated with SLBZ-AP. Pain behavioral tests were performed to explore the effect on BMLC-induced pain in mice. TUNEL staining was used to investigate apoptosis. The mRNA expression of markers in the PI3K/Akt/mTOR pathway was measured by qPCR, and protein expression was detected by western blotting and immunohistochemistry analysis. SLBZ-AP relieved BMLC-induced pain and prolonged animals' survival, promoted cell apoptosis in the marrow from the tibia of BMLC mice, and inhibited mRNA and protein expression of AKT, mTOR, P70S6, and VEGF, as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF upregulation in the marrow of tibia induced by BMLC, an effect which was similar to rapamycin. Our results suggested that SLBZ-AP may have antinociceptive effect and prolong survival of BMLC mice at least partially by inhibiting cell proliferation and promoting apoptosis through the PI3K/Akt/mTOR signaling pathway. SLBZ-AP may be a potential candidate for BMLC therapy.
Highlights
Small- cell lung cancer (SCLC) is one form of lung cancer, which is the leading cause of cancer-related deaths worldwide [1]
high dose group (H-D) Shenling Baizhu additive powder (SLBZ-AP) (60 g·kg−1·day−1) tends to show less effect on p-AKT, p-mTOR, p-P70S6, and VEGF protein expression induced by bone metastasis of lung cancer (BMLC) and the effect of medium dose group (M-D) SLBZ-AP is more than that of low dose group (L-D) SLBZ-AP, which may be due to the fact that the expression of p-AKT, p-mTOR, p-P70S6, and VEGF in the marrow from tibia from bone metastasis with small-cell lung cancer (BMLC) mice was measured and cells in the marrow from tibia might include cancer cells and normal cells. e effect of H-D SLBZ-AP remains to be explored further
PI3K/Akt/mTOR signaling pathway is involved in possible mechanisms of oncogenic transformation as stimulation of proliferation, survival, invasion/metastasis, metabolic reprogramming, and suppression of autophagy and is commonly activated in lung cancer to correlate with cells proliferation and metastasis
Summary
Small- cell lung cancer (SCLC) is one form of lung cancer, which is the leading cause of cancer-related deaths worldwide [1]. Lung cancer tends to develop into bone metastases (BMLC) strongly and about 30–40% of lung cancer patients develop bone metastasis [2,3,4]. Erefore, prevention of BMLC and relieving the pain to improve lung cancer patients’ quality of life are critical. PI3K/Akt/mTOR signaling pathway plays a pivotal role in a variety of biological activities to regulate cell proliferation, survival, and migration [7, 8]. PI3K/Akt/mTOR signaling pathway is one of the major signaling cascades which is frequently activated in various human cancers including lung cancer [10, 11]. It has been confirmed by researchers that suppression of PI3K/Akt/mTOR signaling pathway activation may inhibit cells proliferation and metastasis in lung cancer [12,13,14,15]. PI3K/Akt/mTOR signaling pathway has been considered a promising therapeutic target
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