Schisandrin B Inhibits Multiple Myeloma Growth and Synergizes with Bortezomib in Mice by Modulating `JAK/STAT` and `ROS`

The management of Multiple Myeloma (MM), a formidable hematological malignancy characterized by malignant plasma cells expanding within the bone marrow, continues to pose substantial challenges. Despite advances with agents like melphalan and dexamethasone, MM remains virtually incurable, with many patients facing difficult-to-treat and therapy-refractory disease. Novel strategies are urgently needed to improve patient outcomes and overcome resistance. Schisandrin B (Sch B), a bioactive compound from Traditional Chinese Medicine, has demonstrated potent antitumor properties, making its in vivo effects on MM a critical area of investigation.

Researchers investigated the antitumor effects of Schisandrin B (dose not specified) in a mouse model of Multiple Myeloma. Tumor growth was assessed by measuring body weight and tumor volume. Cell proliferation, cell cycle progression, and apoptosis were analyzed using flow cytometry. ELISA was performed to quantify levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Reactive oxygen species (ROS) were detected via immunofluorescence. Western blotting was used to determine the expression of IL-6, JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3). A combination arm with bortezomib was also included to evaluate synergistic effects.

Schisandrin B markedly inhibited tumor proliferation in mice with Multiple Myeloma, indicating a direct impact on the uncontrolled growth characteristic of malignant cells. This antiproliferative effect was further supported by the induction of S-phase cell cycle arrest, effectively halting the malignant cells' ability to replicate their DNA and divide. Concurrently, Schisandrin B promoted apoptosis, the programmed cell death pathway, leading to the elimination of cancerous cells. These combined actions demonstrate a robust, multi-faceted mechanism by which Schisandrin B targets tumor viability and expansion. Furthermore, the study revealed that Schisandrin B significantly reduced the expression of key pro-inflammatory and pro-angiogenic factors within the tumor microenvironment. Specifically, levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were decreased. IL-6 is a cytokine known to promote MM cell survival and drug resistance, while VEGF is crucial for new blood vessel formation, supporting tumor growth and metastasis. The compound also attenuated the activation of the JAK/STAT signaling pathway, evidenced by reduced phosphorylation of JAK2 (p-JAK2) and STAT3 (p-STAT3). The JAK/STAT pathway is a critical driver of MM cell proliferation, survival, and drug resistance, making its inhibition a significant therapeutic target. > Most importantly, Schisandrin B increased reactive oxygen species (ROS) levels, which can induce oxidative stress and contribute to apoptosis in cancer cells, further enhancing its cytotoxic effects. This increase in ROS alongside JAK/STAT inhibition and IL-6/VEGF reduction paints a comprehensive picture of its antitumor mechanism. Moreover, Schisandrin B exhibited a synergistic antitumor effect when combined with bortezomib, a proteasome inhibitor widely used in MM therapy, suggesting a promising strategy for improving current treatment outcomes by enhancing efficacy and potentially overcoming resistance.